Background: An international group of experts recommended reclassifying non-invasive follicular variant of papillary thyroid cancers (FVPTC) as ‘non-invasive follicular thyroid neoplasm with papillary-like nuclear features’ (NIFTP) in April 2016. The purpose of this study was to establish preoperative clinical, laboratory, ultrasonographic, and cytological variables, which can differentiate NIFTP from FVPTC. Methods: We conducted a retrospective chart review of consecutive patients from a single institution evaluated between January 2012 and December 2017. 203 adult patients underwent lobectomy or total thyroidectomy for a FVPTC during that period. Each patient's medical chart was reviewed and information on pre-operative variables was recorded. An expert pathologist reviewed all surgical specimens and reclassified a subset of FVPTC as NIFTP according to the specific criteria. Results: Overall, 44 patients were included in the NIFTP group and 159 in the non-NIFTP group. Mean age was 50.1 years in the NIFTP group and 50.7 in the non-NIFTP group. Most patients were female (86.4% (38/44) in the NIFTP group vs 79.8% (127/159) in the non-NIFTP group). More patients underwent lobectomy in the NIFTP group (50% (22/44) vs 16.4% (26/159) in the non-NIFTP group, p = < 0.0001). Less patients received radioactive iodine in the NIFTP group (31.8% (14/44) vs 52.2% (83/159) in the non-NIFTP group, p = 0.0177). Preoperative thyroglobulin levels were lower in NIFTP patients (Median 25.55 mcg/L +/− 67.8 vs 76.06 mcg/L +/− 119.8 in Non-NIFTP, p = 0.0104). NIFTP nodules were smaller (Mean size 22.97 mm +/− 12.3 vs 25.88 mm +/− 11.2 for non-NIFTP, p = 0.0448) and more often solid than non-NIFTP (93.2% (41/44) vs 74.8% (119/159) for non-NIFTP, p = 0.0067). 2017 ACR TIRADS nodule category of 1–4 on ultrasound had a negative predictive value and a sensitivity of 100% for NIFTP. ROC Curve Analysis demonstrated that a preoperative thyroglobulin level of 31.3 mcg/L had a sensitivity of 75% and a specificity of 62.5% to differentiate NIFTP from non-NIFTP cancers. Conclusion: Lower preoperative thyroglobulin levels, smaller nodule size, solid texture and 2017 ACR TIRADS Category of 1–4 are more strongly associated with NIFTP than FVPTC and can favour less invasive surgical options such as lobectomy.

Background/Objectives: Molecular testing of thyroid nodules enables the detection of genetic alterations, which can help assess the risk of malignancy and tumor behavior. While telomerase reverse transcriptase (TERTp) mutations are known to be associated with aggressive disease, their exact prognostic significance when occurring alone or with other molecular alterations remains underreported. Methods: This study examined patients with thyroid cancer treated at two tertiary care hospitals from 2017 to 2024. We compared tumor behavior in patients with TERTp molecular alterations occurring alone and with concurrent molecular alterations. Aggressive histologic subtypes were defined as tall-cell, hobnail, and columnar variants of papillary carcinoma, as well as poorly differentiated and anaplastic carcinoma. High-risk disease was defined according to the 2015 ATA guidelines as gross extrathyroidal extension, lymph node metastasis >3 cm, postoperative elevated serum thyroglobulin, distant metastases, and/or positive resection margins. Statistical analysis was performed to assess differences between groups. Results: 30 patients with TERTp-positive thyroid malignancies were included. TERTp/BRAF V600E was the most prevalent mutation combination (n = 13, 43.3%), followed by TERTp alone (n = 8, 26.7%) and TERTp/RAS (n = 7, 23.4%). TERTp/EIF1AX/GNAS and TERTp/EIF1AX/PIK3CA were the least common combinations (n = 1, 3.3% each). Nodules with TERTp and concurrent mutations were significantly more likely to be classified as high-risk (p = 0.006) and were more frequently associated with aggressive histologic subtypes (p = 0.003) compared to those with TERTp mutations alone, which tended to exhibit more benign behavior. Conclusions: Thyroid carcinomas harboring both TERTp and concurrent molecular alterations are associated with more aggressive features and a higher likelihood of being classified as high-risk. In contrast, TERTp mutations occurring alone do not confer an elevated risk.

Importance: ChatGPT has emerged as a medical resource through advanced language processing. Patients with thyroid nodules classified under The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) may use it to complement discussions with physicians. Objective: We aimed to determine whether ChatGPT's recommendations on managing thyroid nodules classified by TBSRTC align with those of experienced thyroid specialists. Setting/Participants: A multidisciplinary panel of 5 thyroid cancer specialists, including otolaryngologists and endocrinologists, from 3 university-affiliated teaching hospitals in Montreal, Canada, evaluated the responses. Intervention/Exposure: ChatGPT-3.5 was prompted with 4 questions for each of the 6 Bethesda categories regarding the meaning and management of thyroid nodules, generating 24 responses for evaluation. Main Outcome/Measures: We assessed ChatGPT’s accuracy against the latest American Thyroid Association (ATA) guidelines using a 4-point Likert scale (90%). Additionally, specialists rated their comfort or reluctance in recommending ChatGPT as a complementary tool for patient discussions. Results: Of the 24 ChatGPT-generated responses, 19 (79.2%) demonstrated moderate to good consistency with the ATA guidelines. The mean consistency score was 3.38/4 and median was 3.5. Consensus (IQR ≤ 1) was achieved in 23 out of 24 responses (95.8%), reflecting strong inter-rater reliability. Consistency scores were highest in Bethesda I–III and declined progressively in higher-risk categories, with the lowest mean score observed in Bethesda VI. Similarly, an upward trend in clinician reluctance was observed from Bethesda I through VI, indicating greater caution in recommending ChatGPT responses for patients suspicious for or diagnosed with malignancy (Bethesda V–VI). Conclusion and Relevance: While ChatGPT’s responses generally align with specialist recommendations, they are not fully reliable. ChatGPT lacks the ability to serve as an independent or accurate source of medical advice for thyroid nodule management. It remains a useful complement for patient discussions, especially in low-risk scenarios, but further improvements are necessary to make it a safe, reliable component of patient care in complex cases.

Background: Neck hematoma following thyroid surgery is a potentially life‐threatening complication.Methods: This retrospective case–control study reviewed neck hematoma reoperations following thyroid surgery (2009–2024), using 3:1 matching. Univariable analysis identified hematoma and delayed onset (≥ 6 h) risk factors, with odds ratios (ORs) and 95% confidence intervals (CIs).Results: Among 5502 surgeries, the hematoma incidence was 0.55% (n = 30). The mean age was 54 and the female‐to‐male ratio was 7:3. Key risk factors included pre‐induction blood pressure > 160 mmHg (OR = 3.04 [95% CI = 1.25–7.39], p = 0.014) and limited blood pressure change postmedication (OR = 6.25 [95% CI = 1.03–38.08], p = 0.047). The hematoma group had higher rates of smoking, hypertension, diabetes, Graves' disease, and prior thyroid surgery, and, in delayed hematoma cases, larger nodules, total thyroidectomy, and central neck dissection, though not statistically significant.Conclusion: Patients with poorly controlled blood pressure may not be candidates for outpatient thyroidectomy.

Importance: BRAF V600E mutations are frequently associated with aggressive papillary thyroid carcinomas (PTCs), yet tumors with low allele frequency (AF) are often considered to be indolent. However, exceptions exist, suggesting additional factors may influence tumor behavior. Gene expression alterations (GEA) may help identify tumors with more aggressive molecular phenotypes. Objective: To evaluate whether aggressive clinicopathologic features are associated with GEA positivity in low AF BRAF V600E -mutated PTCs. Design: Retrospective cohort study. Setting: Two McGill University Academic Hospitals, 2019 to 2024. Participants: Patients with PTC harboring BRAF V600E (AF ≤ 25%) who underwent preoperative testing. Intervention or Exposure: Low AF BRAF V600E mutation (≤25%) characterized using ThyroSeq v3 genomic classifier. Main Outcome Measures: The primary outcome was GEA status. Tumor aggressiveness (defined by extrathyroidal extension, lymph node metastasis, lymphovascular invasion, high-risk histology, or aggressive variants), Bethesda classification, and AF were evaluated as predictors of GEA using logistic regression. Stratified analysis was performed based on AF (≤10% vs. >10%). Results: Among 49 patients identified (mean age 49 ± 14 years; 86% female; mean AF 11% ± 8%), 73% (36/49) had aggressive features and 61% (30/49) had GEA-positive tumors. Among GEA-positive tumors, 80% (24/30) were classified as aggressive and had a significantly-higher median AF (16.5%) than GEA-negative tumors ( P = .0003). Stratified analysis showed that Bethesda VI nodules significantly predicted GEA positivity in tumors with AF > 10% ( P = .03). Conclusion: In low AF BRAF V600E-mutated PTCs, GEA positivity is associated with high-risk cytology, higher AF, and aggressive tumor features. Relevance: GEA may be a useful molecular marker of aggressive tumor biology in low AF PTCs and holds potential as a complementary tool for preoperative risk stratification.

Background/Objectives: RAS mutations are among the most common genetic alterations in thyroid cancer and are generally associated with less aggressive behavior. However, when co-occurring with TERT (telomerase reverse transcriptase) promoter mutations, known markers of poor prognosis, tumors exhibit markedly more aggressive features. The allele frequency (AF) of RAS may serve as a potential indicator of clonal dominance and the likelihood of additional high-risk mutations, such as TERT mutation. This study aims to assess whether a high RAS AF correlates with the presence of coexisting TERT promoter mutations and other molecular alterations. Methods: A retrospective chart review was performed on 111 patients with thyroid nodules harboring RAS mutations, either alone or in combination with TERT promoter mutations. All patients underwent molecular testing with ThyroSeq v3 and subsequent thyroidectomy at McGill University teaching hospitals. RAS AF was analyzed in relation to TERT mutation status, nodule size, and other molecular alterations including copy number alterations (CNA) and gene expression profiles (GEP). Results: The mean RAS AF was significantly higher in nodules with both RAS and TERT mutations (38.1%) compared to those with RAS mutations alone (22.1%) (p = 0.002). Nodules with coexisting TERT mutations were also significantly larger (mean size: 3.7 cm vs. 2.4 cm; p = 0.005). Malignant nodules, regardless of TERT status, showed a trend toward higher RAS AF than benign nodules (23.0% vs. 16.3%; p = 0.052). Higher RAS AF was also associated with the presence of CNA and/or GEP positivity. Notably, GEP was positive in 100% of nodules with both RAS and TERT mutations, compared to 37.5% in RAS-only nodules (p = 0.002). Conclusions: A high RAS AF increases the likelihood of a TERT promoter mutation and other genetic alterations, highlighting the importance of RAS AF in optimizing patient care and management.