Feasibility of whole-exome sequencing in fine-needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations.

Genetic profiling is important for assisting the management of papillary thyroid microcarcinoma (PTMC). Although whole-exome sequencing (WES) of surgically resected PTMC tissue has been performed and revealed potential prognostic biomarkers, its application in PTMC fine-needle aspiration (FNA) specimens has not been explored. This study aimed to evaluate the feasibility of WES using FNA specimens of PTMC. Five PTMC patients were enrolled with clinical characteristics gathered. Fine aspiration cytology needle (23 gauges) was used to collect FNA biopsy with ultrasound guidance. WES analysis of FNA specimens from five PTMC patients and matched blood samples was performed. The WES of FNA samples yielded an average sequencing depth of 281× and average coverage of 99.5%. We identified 534 somatic single-nucleotide variants and 13 indels in total, and per sample, we found a mean of 24 exonic mutations, which affected a total of 120 genes. In the PTMC FNA samples, the most frequently mutated genes were BRAF and ANKRD18B, and the four driver genes were BRAF, AFF3, SRCAP, and EGFR. We also identified several germline cancer predisposing gene mutations. The results suggest that WES of FNA specimens is feasible for PTMC and can identify novel genetic mutations.

Thirty years of active surveillance for low-risk thyroid cancer, lessons learned and future directions.

Active Surveillance is a non-invasive strategy designed to identify a minority of patients with low-risk papillary thyroid carcinoma who might experience clinical progression and benefit from additional definitive treatments. Global experience suggests that these tumors typically show minimal changes in size during active surveillance, often demonstrating very slow growth or even size reduction. Moreover, the rate of lymph node metastases is low and can be effectively managed through rescue surgery, without impacting cancer-related mortality. However, despite 30 years of experience demonstrating the safety and feasibility of active surveillance for appropriately selected patients, this approach seems to have limited adoption in specific contexts. This limitation can be attributed to various barriers, including disparities in access to accurate information about the indolent nature of this disease and the prevalence of a maximalist mindset among certain patients and medical settings. This review aims to revisit the experience from the last three decades, provide current insights into the clinical outcomes of active surveillance trials, and propose a systematic approach for its implementation. Furthermore, it intends to emphasize the importance of precise patient selection and provides new perspectives in the field.

A nomogram for predicting adverse pathologic features in low-risk papillary thyroid microcarcinoma.

BACKGROUND: Identifying risk factors for adverse pathologic features in low-risk papillary thyroid microcarcinoma (PTMC) can provide valuable insights into the necessity of surgical or non-surgical treatment. This study aims to develop a nomogram for predicting the probability of adverse pathologic features in low-risk PTMC patients. METHODS: A total of 662 patients with low-risk PTMC who underwent thyroid surgery were retrospectively analyzed in Qilu Hospital of Shandong University from May 2019 to December 2021. Logistic regression analysis was used to determine the risk factors for adverse pathologic features, and a nomogram was constructed based on these factors. RESULTS: Most PTMC patients with these adverse pathologic features had tumor diameters greater than 0.6 cm (p < 0.05). Other factors (age, gender, family history of thyroid cancer, history of autoimmune thyroiditis, and BRAFV600E mutation) had no significant correlation with adverse pathologic features (p > 0.05 each). The nomogram was drawn to provide a quantitative and convenient tool for predicting the risk of adverse pathologic features based on age, gender, family history of thyroid cancer, autoimmune thyroiditis, tumor size, and BRAFV600E mutation in low-risk PTMC patients. The areas under curves (AUC) were 0.645 (95% CI 0.580-0.702). Additionally, decision curve analysis (DCA) and calibration curves were used to evaluate the clinical benefits of this nomogram, presenting a high net benefit. CONCLUSION: Tumor size > 0.60 cm was identified as an independent risk factor for adverse pathologic features in low-risk PTMC patients. The nomogram had a high predictive value and consistency based on these factors.

Development of a nomogram for prediction of central lymph node metastasis of papillary thyroid microcarcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most frequent malignant tumor in thyroid carcinoma. The aim of this study was to explore the risk factors associated with central lymph node metastasis in papillary thyroid microcarcinoma (PTMC) and establish a nomogram model that can assess the probability of central lymph node metastasis (CLNM). METHODS: The clinicopathological data of 377 patients with cN0 PTMC were collected and analyzed from The Second Affiliated Hospital of Fujian Medical University from July 1st, 2019 to December 30th, 2021. All patients were examined by underwent ultrasound (US), found without metastasis to central lymph nodes, and diagnosed with PTMC through pathologic examination. All patients received thyroid lobectomy or total thyroidectomy with therapeutic or prophylactic central lymph node dissection (CLND). R software (Version 4.1.0) was employed to conduct a series of statistical analyses and establish the nomogram. RESULTS: A total of 119 patients with PTMC had central lymph node metastases (31.56%). After that, age (P < 0.05), gender (P < 0.05), tumor size (P < 0.05), tumor multifocality (P < 0.05), and ultrasound imaging-suggested tumor boundaries (P < 0.05) were identified as the risk factors associated with CLNM. Subsequently, multivariate logistic regression analysis indicated that the area under the receiver operating characteristic (ROC) curve (AUC) of the training cohort was 0.703 and that of the validation cohort was 0.656, demonstrating that the prediction ability of this model is relatively good compared to existing models. The calibration curves indicated a good fit for the nomogram model. Finally, the decision curve analysis (DCA) showed that a probability threshold of 0.15-0.50 could benefit patients clinically. The probability threshold used in DCA captures the relative value the patient places on receiving treatment for the disease, if present, compared to the value of avoiding treatment if the disease is not present. CONCLUSION: CLNM is associated with many risk factors, including age, gender, tumor size, tumor multifocality, and ultrasound imaging-suggested tumor boundaries. The nomogram established in our study has moderate predictive ability for CLNM and can be applied to the clinical management of patients with PTMC. Our findings will provide a better preoperative assessment and treatment strategies for patients with PTMC whether to undergo central lymph node dissection.

Follow-up strategy of radiofrequency ablation for papillary thyroid microcarcinoma: defining a response-to-ablation system.

OBJECTIVE: To define a response-to-ablation system based on dynamic risk stratification proposed by the 2015 American Thyroid Association guidelines for predicting clinical outcomes and guiding follow-up strategies for patients with low-risk papillary thyroid microcarcinoma (PTMC) who underwent radiofrequency ablation (RFA). METHODS: This retrospective study reviewed patients with low-risk PTMC who underwent RFA between 2014 and 2018. We classified patients into three groups based on their response to therapy at the 1-year follow-up: complete, indeterminate, and incomplete. The primary endpoints were local tumor progression (LTP) and disease-free survival (DFS). RESULTS: Among the 748 patients (mean age, 43.7 years ± 9.8; 586 women), 4.0% (30/748) had LTP during a median follow-up of 5 years. The response was complete in 80.2% (600/748) of the patients, indeterminate in 18.1% (135/748), and incomplete in 1.7% (13/748). The LTP rate in the final follow-up was 1% (6/600), 8.1% (11/135), and 100% (13/13), respectively. The risk of LTP was significantly different in the incomplete response group (HR, 1825.82; 95% CI: 458.27, 7274.36; p < 0.001) and indeterminate response group (HR, 8.12; 95% CI: 2.99, 22.09; p < 0.001) than in the complete response group. There were significant differences in DFS among groups (p < 0.001). The proportion of variation explained and C-index of the system was high (27.66% and 0.79, respectively). CONCLUSIONS: We defined a response-to-ablation system that provides a new paradigm for the management of patients with PTMC who underwent RFA. Our data confirm that the system can effectively predict the risk of LTP and guide ongoing follow-up recommendations. KEY POINTS: • The response-to-ablation system can classify patients with low-risk PTMC who underwent RFA into complete, indeterminate, or incomplete response categories. • Results suggest that, in this population, this system can identify three separate cohorts of patients who have significantly different clinical outcomes. • The response-to-ablation system will help better tailor the ongoing follow-up recommendations.

The relationship between ablation range and ablation energy in papillary thyroid microcarcinoma: a comparison between microwave ablation and laser ablation.

OBJECTIVES: To study the relationship between the ablation range and applied energy of laser ablation (LA) and microwave ablation (MWA) in papillary thyroid microcarcinoma (PTMC). METHODS: A total of 201 PTMC patients were treated with LA (n = 102) or MWA (n = 99) with single-applicator fixed ablation. The ablation range was determined by contrast-enhanced ultrasound. The ratios of ablation volume, longitudinal diameter, and orthogonal diameter to ablation energy (RAV/E, RAL/E, RAO/E) were analyzed and compared between MWA and LA. The effects of PTMC characteristics and Hashimoto's thyroiditis (HT) on ablation efficiency were evaluated by linear regression. RESULTS: The RAV/E was 0.72 (0.65-0.84) mm3/J for MWA and 0.48 (0.39-0.54) mm3/J for LA. HT was significantly correlated with RAV/E of LA (coefficient = - 0.367, p < 0.0001). RAL/E did not differ significantly between MWA and LA (MWA 0.026 mm/J, LA 0.025 mm/J; p = 0.957). However, MWA had a greater RAO/E than LA (MWA 0.014 mm/J, LA 0.012 mm/J; p < 0.0001). The plateau values of MWA and LA on the ablation orthogonal diameter were 10.7 mm and 8.69 mm, respectively. CONCLUSIONS: MWA showed a higher RAV/E than LA. More intuitively, MWA had a better ablation performance than LA on the orthogonal axis rather than the longitudinal axis. Theoretically, MWA and LA could achieve complete ablation of ≤ 6.70 mm and ≤ 4.69 mm PTMC separately by single-applicator fixed ablation considering a unilateral 2-mm safe margin. HT had a negative effect on LA but not on MWA. CLINICAL RELEVANCE STATEMENT: This study establishes strong connections between ablation energy and ablation range in papillary thyroid microcarcinoma (PTMC) in vivo, possibly contributing to the supplementation of the PTMC Ablation Consensus or Guidelines and providing a scientific basis for choosing clinical ablation parameters in PTMC. KEY POINTS: • Both microwave ablation (MWA) and laser ablation (LA) have excellent performance on the ablation longitudinal axis (easily exceeding 10 mm) for papillary thyroid microcarcinoma (PTMC). • MWA performed much better than LA on the ablation orthogonal axis. • MWA and LA are expected to achieve complete ablation of ≤ 6.70 mm and ≤ 4.69 mm PTMC separately by single-applicator fixed ablation considering a unilateral 2-mm safe margin.

Radiofrequency ablation for capsular-located versus noncapsular-located papillary thyroid microcarcinoma: a propensity score matching study of 1095 patients.

OBJECTIVES: To assess the safety and efficacy of radiofrequency ablation (RFA) for capsular-located papillary thyroid microcarcinoma (PTMC) in a large cohort and to compare its outcomes with those of noncapsular-located PTMC. METHODS: We retrospectively reviewed patients who underwent RFA for solitary capsular-located and noncapsular-located low-risk PTMC (n = 1095) from June 2014 to October 2020. To balance confounding variables between capsular and noncapsular groups, we employed the 1:1 propensity score matching approach. We evaluated and compared tumor changes, disease progression, and complications in both groups. Furthermore, we analyzed the association between capsular location and disease progression using multivariable Cox regression. RESULTS: During a mean follow-up time of 29.86 ± 16.14 months and 29.73 ± 15.69 months, no substantial difference was observed between capsular and noncapsular groups in the latest volume (0.83 ± 3.66 mm3 vs. 0.85 ± 3.67 mm3, p = 0.44) and volume reduction ratio (99.29 ± 4.04% vs. 99.43 ± 3.03%, p = 0.43), and cumulative disappearance rate (87.87% vs. 86.07%, p = 0.31). In addition, no significant differences were observed in complication incidence (1.35% vs. 1.12%, p = 0.76) and progression-free survival (p = 0.53). Based on adjusted multivariate Cox proportional hazard analysis, the association between capsular location and disease progression was nonsignificant (all p > 0.05). CONCLUSION: This study demonstrates that the short-term outcomes of RFA for capsular-located PTMCs are comparable to those of noncapsular-located PTMCs. These findings indicate that RFA may be a viable and effective alternative for eligible patients with solitary capsular-located PTMC. CLINICAL RELEVANCE STATEMENT: Radiofrequency ablation may serve as a safe and effective alternative treatment method for eligible patients with capsular-located and noncapsular-located papillary thyroid microcarcinoma. KEY POINTS: • The safety and efficacy of radiofrequency ablation for capsular-located and noncapsular-located papillary thyroid microcarcinomas were comparable. • Disease progression did not differ significantly between capsular-located and noncapsular-located papillary thyroid microcarcinomas. • The incidence of complications for capsular-located papillary thyroid microcarcinoma was low.

Radiofrequency ablation for papillary thyroid microcarcinoma with a trachea-adjacent versus trachea-distant location.

OBJECTIVE: To evaluate the outcomes of radiofrequency ablation (RFA) for papillary thyroid microcarcinoma (PTMC) adjacent to the trachea and compare them with those of PTMC distant from the trachea. METHODS: Patients who received RFA for solitary low-risk PTMC between June 2014 and July 2020 were reviewed and classified into adjacent and distant groups. To balance between-group confounders, the propensity score matching approach was employed. Volume, volume reduction ratio (VRR), tumor disappearance, complications, and disease progression were assessed and compared between the groups. Furthermore, factors affecting disease progression were evaluated. RESULTS: A total of 122 and 470 patients were included in the adjacent and distant groups, respectively. Overall VRR was 99.5% ± 3.1 and cumulative tumor disappearance rate was 99.4% after a mean follow-up time of 40.1 months ± 16.2. Overall disease progression and complications incidence were 3.7% and 1.0%, respectively. No substantial differences were observed between the two groups in the latest volume (0.8 mm3 ± 4.1 vs. 0.9 mm3 ± 4.2, p = .77), VRR (99.7% ± 1.6 vs. 99.5% ± 2.7, p = .75), cumulative tumor disappearance rate (92.6% vs. 94.2%, p = .58), and incidence of disease progression (4.1% vs. 4.5%, p = .70) and complication (1.7% vs. 0.8%, p = .86) after 1:2 matching. Additionally, tracheal adjacency exhibited no association with disease progression in multivariate Cox regression analysis (p = .73). CONCLUSION: For eligible patients with PTMC located adjacent to or distant from the trachea, RFA may offer a safe and effective alternative treatment method.

Comparison of the efficacy and safety of ultrasound-guided radiofrequency ablation and microwave ablation for the treatment of unifocal papillary thyroid microcarcinoma: a retrospective study.

PURPOSE: This study aimed to compare the efficacy and safety of ultrasound-guided RFA and MWA in the treatment of unifocal PTMC. METHODS: This retrospective study included 512 patients with 512 unifocal papillary thyroid microcarcinomas (PTMCs) who underwent RFA (n = 346) and MWA (n = 166) between January 2021 and December 2021. The volumes of the ablation areas were measured during follow-up, and the volume reduction rates were evaluated. The ablation duration, volume of hydrodissection, and ablation-related complications were also compared between the groups. RESULTS: All lesions received complete ablation and no local or distant recurrences were observed in the two groups. A larger volume of isolation liquid was used for RFA than for MWA (p = 0.000). Hoarseness occurred in seven patients who underwent RFA (p = 0.102). At the 1-week follow-up, the mean volume of the areas ablated by RFA was smaller than that of the areas ablated by MWA (p = 0.049). During follow-ups at months 3, 9, 12, 15, and 18, the mean volumes of the ablated areas were larger in the RFA group than in the MWA group (all, p < 0.05). The mean volume of the ablated lesions increased slightly at the 1-week follow-up and then decreased at 1 month after ablation in both groups. The absorption curve of the ablated lesions in the RFA group was similar to that in the MWA group. CONCLUSIONS: RFA and MWA are both efficient and safe methods for treating unifocal PTMC. They may be alternative techniques for patients who are not eligible or are unwilling to undergo surgery.

Conformal thyroidectomy is a feasible option in papillary thyroid microcarcinoma: a retrospective cohort study with 10-year follow-up results.

BACKGROUND: In recent years, there has been an increasing prevalence of patients with papillary thyroid microcarcinoma (PTMC) without lymph node involvement in medical centers worldwide. For patients who are unable to undergo active surveillance (AS) and are afraid of postoperative complications, conformal thyroidectomy may be a suitable option to ensure both preservation of function and complete removal of the tumor. METHODS: The patients in the cohort during 2010 to 2015 were retrospectively enrolled strictly following the inclusion and exclusion criteria. The observation and control groups were defined based on the surgical approach, with patients in the observation group undergoing conformal thyroidectomy and patients in the control group undergoing lobectomy. Event-free survival (EFS), the interval from initial surgery to the detection of recurrent or metastatic disease, was defined as the primary observation endpoint. RESULTS: A total of 319 patients were included in the study, with 124 patients undergoing conformal thyroidectomy and 195 patients undergoing lobectomy. When compared to lobectomy, conformal thyroidectomy demonstrated reduced hospital stays, shorter operative times, and lower rates of vocal cord paralysis and hypoparathyroidism. Furthermore, the mean bleeding volume during the operation and the rate of permanent hypothyroidism were also lower in the conformal thyroidectomy group than in the lobectomy group. However, there was no statistically significant difference observed in the 5- and 10-year EFS between the two groups. CONCLUSIONS: Conformal thyroidectomy had advantages in perioperative management and short-term complication rates, with an EFS that was not inferior to that of lobectomy. Thus, conformal thyroidectomy is a feasible option for low-risk PTMC patients.

Active surveillance for adult low-risk papillary thyroid microcarcinoma-a review focused on the 30-year experience of Kuma Hospital.

Active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC), which was initiated at Kuma Hospital (Kobe, Japan) in 1993 and Cancer Institute Hospital (Tokyo) in 1995, is now gradually being adopted worldwide, and several prospective studies have described the favorable outcomes of PTMC patients who underwent AS. The most important factor predicting PTMC growth is young age, and PTMC enlargement in young patients may be affected by high serum levels of thyroid-stimulating hormone. This review notes that one patient showed lung metastasis after conversion surgery (CS) following AS, but there are no reports of patients dying of thyroid carcinoma during or after AS. Some PTMCs enlarge or show newly appeared metastatic nodes requiring CS, and findings on the postoperative prognosis and incidence of significant surgical complications (e.g., permanent vocal cord paralysis, hypoparathyroidism) do not differ significantly between patients who underwent CS after AS and those who underwent immediate surgery (IS). IS has been associated with significantly higher incidences of these complications compared to AS as the initial management. Several studies have examined the quality of life (QoL) of patients who underwent AS versus IS, and reported discrepant findings regarding various psychological conditions (including anxiety). Medical costs for AS and IS vary regionally, and in Japan, the 10-year total cost of IS was 4.1 times greater than that of AS in 2017. Taken together, the existing findings demonstrate that AS can be appropriate for the initial management of patients with PTMC.

Papillary thyroid microcarcinoma: Does management differ based on facility variables?

PURPOSE: Papillary thyroid carcinoma detection has increased dramatically in the United States. However, the indolent nature of papillary thyroid microcarcinoma (mPTC) has led the American Thyroid Association (ATA) to advocate for more conservative management. The 2015 ATA recommendations advocated for observation or lobectomy for mPTC. However, the majority of mPTCs continue to be treated with more aggressive surgical management. In this study, we aim to understand the management of mPTC based on facility variables. MATERIALS AND METHODS: A retrospective observational study of patients diagnosed with mPTC between 2004 and 2018 was performed using the National Cancer Database incidence data. We collected data on patient sex, age, tumor size, race, ethnicity, geographic location, thyroid surgical volume at the facility, and treatment modality for mPTC were collected. Conservative and non-conservative treatment modalities based on patient and facility characteristics were compared both longitudinally and cross-sectionally between pre- and post-2015 ATA recommendations. RESULTS: Total thyroidectomy with or without radioactive iodine ablation (RAI) remains the treatment of choice regardless of patient and facility characteristics. Patients treated at low-volume facilities were actually more likely to be treated conservatively. CONCLUSIONS: Despite 2015 ATA recommendations advocating for observation or lobectomy for mPTC, patients with mPTC are still more likely to be treated with total thyroidectomy with or without RAI, especially at high-volume facilities.

Efficacy and safety of laser ablation and microwave ablation to treat papillary thyroid microcarcinoma: A retrospective study.

OBJECTIVE: To retrospectively analyze the efficacy and safety of laser ablation (LA) and microwave ablation (MWA) in the treatment of papillary thyroid microcarcinoma (PTMC). METHODS: This was a retrospective study of 103 patients (109 nodules) who underwent thermal ablation for PTMC between October 2019 and March 2023; 61 underwent LA and 48 underwent MWA. The mean patients' age was 43.50 ± 12.42 years. After ablation, changes in tumor size at different time points, local recurrence, new lesions, lymph node metastasis, and complications were evaluated and recorded. The feasibility, success rate, and safety of LA and MWA were analyzed. RESULTS: Complete absence of enhancement on contrast-enhanced ultrasonography was observed in all target tumors after ablation. At the last follow-up, the mean volume of the PTMC nodules decreased from 0.09 ± 0.09 to 0.03 ± 0.03 ml (LA group) and from 0.11 ± 0.10 to 0.06 ± 0.08 ml (MWA group) (both, P < 0.05). There was no significant difference in volume change between the groups (P (groups): 0.520; P (groups over time): 0.423), indicating similar efficacy between the groups. There was also no significant difference in the volume reduction rate between the groups during follow-up, except for at 3 months (P = 0.023). The complication rates did not differ between the LA group (8.2 %) and MWA group (6.3 %) (P > 0.05). CONCLUSION: During the short-term follow-up, ultrasound-guided LA and MWA were effective and safe for PTMC, and there were no significant differences in treatment outcomes between the methods.

Comparative efficacy of different thermal ablation and conventional surgery for the treatment of Papillary Thyroid Microcarcinoma: Systematic review including traditional pooling and Bayesian network meta-analysis.

PURPOSE: To compare the efficacy of different thermal ablation and conventional surgery for the treatment of Papillary Thyroid Microcarcinoma, using a systematic review including traditional pooling and Bayesian network meta-analysis. MATERIALS AND METHODS: A comprehensive literature search in PubMed, EMBASE, and the Cochrane Library databases identified retrospective studies evaluating the tumor volume change after different thermal ablation or conventional surgery. Studies from the date of their inception to January 6, 2024, were included. A review of 4463 potential papers, including a full-text review of 23, identified 10 eligible papers covering a total of 2658 patients for meta-analysis. The tumor volume change over a 12-month follow-up was compared between different thermal ablations. Tumor diameter change, complications, recurrence, operation and hospitalization time were evaluated by network meta-analysis. RESULTS: Based on the traditional frequentist approach, the overall pooled estimates for the standardized mean difference (SMD) in tumor volume change of radiofrequency ablation (RFA), laser ablation (LA), and microwave ablation (MWA) were 1.38 (95 % credibility interval (CI), 0.62-2.13), 1.94 (95%CI, 0.78-3.10) and 1.38 (95%CI, 1.01-1.75), respectively. Based on the Bayesian network meta-analysis, in examining the surface under the cumulative ranking area (SUCRA) ranking, RFA (SUCRA, 76.6), MWA (SUCRA, 66.6), and LA (SUCRA, 39.8) were identified as the three interventions that were associated with the greatest reduction in risk for complications compared with conventional surgery (CS), with RFA (SUCRA, 76.6) being ranked as the highest in safety. MWA, SMD 4.43 [95%CI, 2.68-6.17], RFA SMD 4.24 [95 % CI, 1.66-6.82], and LA SMD 4.24 [95 % CI, 1.48-7.00] were associated with the shorter operation time compared with CS. LA SMD 4.61 [95 % CI, 1.79-7.44] and MWA SMD 3.07 [95 % CI, 1.32-4.83] were associated with the shorter hospitalization time compared with CS, with LA (SUCRA, 86.5) yielding the highest ranking. MWA was associated with a reduced risk for tumor recurrence RR 0.02 [95 % CI, -0.44-0.49], compared with CS. CONCLUSION: We conducted a comprehensive review of the published literature on the effectiveness and safety of different thermal ablation techniques and conventional surgery for papillary thyroid microcarcinoma. Important research gaps persist due to a lack of long-term data and high-quality randomized controlled trials (RCTs).

The frequency of risk pathological characteristics in clinically low-risk papillary thyroid microcarcinoma suitable for active surveillance.

PURPOSE: Active surveillance has emerged as an initial management strategy for patients with low-risk papillary thyroid microcarcinoma (PTMC). The main objective of this research was to investigate the frequency of risk pathological characteristics among patients with clinically low-risk PTMC who are suitable for Active Surveillance. METHODS: A retrospective review was conducted on patients who underwent lobectomy for PTMC between January 2013 and December 2018. Patients with bilateral tumors, macroscopic multifocal tumors, macroscopic extrathyroidal extension (ETE), clinical lymph node metastases, macroscopic extranodal extension (ENE), distant metastases, a history of neck radiation or familial thyroid cancer were excluded. Pathological characteristics were collected from the postoperative pathological results. Aggressive variants, multifocality, ETE, lymphovascular invasion (LVI), perineural invasion (PNI), metastatic lymph nodes (LNs) ≥ 5, and ENE were defined as risk characteristics. RESULTS: The study included 4923 patients, of whom 1229 (25.0%) were male. The mean age was 43 years. A total of 2250 patients (45.7%) exhibited risk characteristics. Among them, 15 patients presented with aggressive variants, and 1813 patients (36.8%) had ETE. Multifocality, LVI, and PNI were observed in 551 (11.2%), 21 (0.4%), and 40 (0.8%) patients, respectively. A total of 139 patients (2.8%) had five or more metastatic LNs, and ENE was identified in 140 patients. Notably, 172 patients (3.5%) fulfilled the criteria for completion thyroidectomy, as they had aggressive variants, LVI, or five or more metastatic LNs. CONCLUSIONS: Nearly half of the patients diagnosed with clinically low-risk PTMC exhibited risk pathological characteristics, and a small proportion of patients met the criteria for completion thyroidectomy.

Papillary microcarcinoma of the thyroid gland: Evaluation of TERT and BRAFV-600E expression and their relationship with clinicopathological findings.

Papillary microcarcinomas (PMCs) are papillary carcinomas ≤1 cm in size, with an increasing incidence. Although generally indolent, some cases exhibit aggressive behavior. Recently, active surveillance has been recommended to avoid surgical treatment. Identifying molecular changes that predict aggressiveness in PMCs has gained importance, but studies are limited. We aimed to demonstrate TERT expression and BRAF V600E positivity immunohistochemically in PMCs and correlate them with histomorphological features, subtypes, and clinicopathological findings. We included 95 PMC cases diagnosed between 2010 and 2019 at the Department of Pathology, Faculty of Medicine, XXX University. We investigated TERT expression using RT-PCR. We evaluated BRAF V600E mutation immunohistochemically. We evaluated the relationship between genetic, histomorphological, and clinicopathological findings. In patients with multifocality and those with a tumor size ≥0.5 cm, the frequency of lymph node metastasis was significantly higher. A positive correlation was shown between BRAF V600E positivity and lymph node metastasis, lymphovascular invasion, advanced disease stage, and classical subtype by univariate analyses. We detected TERT expression in 18 of 95 patients (7.8 %). No relationship could be detected between TERT expression alone or combined with BRAF positivity and clinicopathological features. Although TERT mutations are associated with aggressiveness in thyroid cancers, this association was absent in PMCs. The presence of TERT expression was demonstrated in some cases. However, TERT expression could not be associated with clinicopathological findings, which is consistent with the literature suggesting that TERT plays a role in advanced stages of carcinogenesis.

Artificial neural network prediction of postoperative complications in papillary thyroid microcarcinoma based on preoperative ultrasonographic features.

OBJECTIVE: To predict post-thyroidectomy complications in papillary thyroid microcarcinoma (PTMC) patients using a deep learning model based on preoperative ultrasonographic features. This study addresses the global rise in PTMC incidence and the challenges in treatment decision-making with high-resolution ultrasonography. METHOD: This study enrolled 1638 patients with clinically staged cN0 PTMC who received surgical treatment from 1997 to 2019 at Beijing Friendship Hospital. Deep learning model was developed using fully connected neural network. Feature selection included 1000 iterations of Bootstrap sampling and Recursive Feature Elimination (RFE) to identify the top 10 features. Data preprocessing involved normalization and imputation for missing values. SMOTE addressed class imbalance. The model was trained and tested on random data split, with performance metrics including Accuracy (ACC), Area Under the Curve (AUC), Sensitivity (SEN), and Specificity (SPE), visualized through a ROC curve and confusion matrix. RESULTS: The fully connected deep neural network model demonstrated high accuracy (ACC 0.81), Area Under the Curve (AUC 0.74), sensitivity (SEN 0.65), and specificity (SPE 0.83) and visualized by ROC curve and confusion matrix. These results highlight the model's reliability and potential as an effective tool in predicting postoperative complications and assisting in clinical decision-making for PTMC patients. CONCLUSION: This study highlights the potential of deep learning in enhancing medical predictions and personalized healthcare. Despite promising results, limitations include a single-center data source and unconsidered factors like lifestyle and genetics. Future research should expand data sources, include more influencing factors, and refine algorithms to improve accuracy and applicability in thyroid cancer treatment.

Frequency of Thyroid Microcarcinoma in Patients Who Underwent Total Thyroidectomy with Benign Indication-A 5-Year Retrospective Review.

Background and Objectives: Incidental thyroid cancers (ITCs) are often microcarcinomas. The most frequent histologic type is a papillary microcarcinoma. Papillary thyroid microcarcinomas are defined as papillary thyroid tumours measuring less than 10 mm at their greatest diameter. They are clinically occult and frequently diagnosed incidentally in histopathology reports after a thyroidectomy. The aim of this study is to evaluate the rate of papillary thyroid microcarcinomas (PTMC) in patients who were thyroidectomised with indications of benign disease. Materials and Methods: We retrospectively evaluated the histological incidence of PTMC in 431 consecutive patients who, in a 5 year period, underwent a thyroidectomy with benign indications. Patients with benign histology and with known or suspected malignancy were excluded. Results: Histopathology reports from 540 patients who underwent a total thyroidectomy in our department between 2016 and 2021 were reviewed. A total of 431 patients were thyroidectomised for presumed benign thyroid disease. A total of 395 patients had confirmed benign thyroid disease in the final histopathology, while 36 patients had incidental malignant lesions (33 PTMC-7.67%, one multifocal PTC without microcarcinomas-0.23%, two follicular thyroid carcinoma-0.46%). Out of the PTMC patients, 29 were female and four were male (7.2:1 female-male ratio). The mean age was 54.2 years old. A total of 24 out of 33 patients had multifocal lesions, 11 of which co-existed with macro PTC. Nine patients had unifocal lesions. A total of 21 of these patients were initially operated on for multinodular goitre (64%), while 13 were operated on for Hashimoto/Lymphocytic thyroiditis (36%). Conclusions: PTMC-often multifocal-is not an uncommon, incidental finding after thyroidectomy for benign thyroid lesions (7.67% in our series) and often co-exists with other incidental malignant lesions (8.35% in our series). The possibility of an underlying papillary microcarcinoma should be taken into account in the management of patients with benign-especially nodular-thyroid disease, and total thyroidectomy should be considered.

Deep learning prediction model for central lymph node metastasis in papillary thyroid microcarcinoma based on cytology.

Controversy exists regarding whether patients with low-risk papillary thyroid microcarcinoma (PTMC) should undergo surgery or active surveillance; the inaccuracy of the preoperative clinical lymph node status assessment is one of the primary factors contributing to the controversy. It is imperative to accurately predict the lymph node status of PTMC before surgery. We selected 208 preoperative fine-needle aspiration (FNA) liquid-based preparations of PTMC as our research objects; all of these instances underwent lymph node dissection and, aside from lymph node status, were consistent with low-risk PTMC. We separated them into two groups according to whether the postoperative pathology showed central lymph node metastases. The deep learning model was expected to predict, based on the preoperative thyroid FNA liquid-based preparation, whether PTMC was accompanied by central lymph node metastases. Our deep learning model attained a sensitivity, specificity, positive prediction value (PPV), negative prediction value (NPV), and accuracy of 78.9% (15/19), 73.9% (17/23), 71.4% (15/21), 81.0% (17/21), and 76.2% (32/42), respectively. The area under the receiver operating characteristic curve (value was 0.8503. The predictive performance of the deep learning model was superior to that of the traditional clinical evaluation, and further analysis revealed the cell morphologies that played key roles in model prediction. Our study suggests that the deep learning model based on preoperative thyroid FNA liquid-based preparation is a reliable strategy for predicting central lymph node metastases in thyroid micropapillary carcinoma, and its performance surpasses that of traditional clinical examination.

Multi-omics profiling of papillary thyroid microcarcinoma reveals different somatic mutations and a unique transcriptomic signature.

BACKGROUND: Papillary thyroid microcarcinoma (PTMC) incidence has significantly increased, and some cases still exhibit invasive traits. The entire molecular landscape of PTMC, which can offer hints for the etiology of cancer, is currently absent. METHODS: We compared our findings with those for PTMC in the TCGA by analyzing the largest study at the current stage of whole exome sequencing and RNA-sequencing data from 64 patients with PTMC. Then, we systematically demonstrated the differences between the two PTMC subtypes based on multi-omics analyses. Additionally, we created a molecular prediction model for the PTMC subtypes and validated them among TCGA patients for individualized integrative assessment. RESULTS: In addition to the presence of BRAF mutations and RET fusions in the TCGA cohort, we also discovered a new molecular signature named PTMC-inflammatory that implies a potential response to immune intervention, which is enriched with AFP mutations, IGH@-ext fusions, elevated immune-related genes, positive peroxidase antibody, and positive thyroglobulin antibody. Additionally, a molecular prediction model for the PTMC-inflammatory patients was created and validated among TCGA patients, while the prognosis for these patients is poor. CONCLUSIONS: Our findings comprehensively define the clinical and molecular features of PTMC and may inspire new therapeutic hypotheses.