Objectives: Thyroid nodules classified as atypia of undetermined significance (AUS) within the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) present a diagnostic challenge, with a risk of malignancy (ROM) of 5% to 50%. In 2017, TBSRTC introduced AUS subcategories to enhance ROM assessment. This study explores the correlation between AUS subclassification, molecular mutations, and surgical outcomes. Methods: Retrospective analysis was performed of 114 AUS cases with molecular profiling by ThyroSeqV3 and surgical follow‐up. AUS subcategories as defined by TBSRTC included: AUS‐Architectural, AUS‐Nuclear, AUS‐Nuclear and Architectural, and AUS‐Hürthle cell. Pathology diagnoses were categorised as benign, malignant, or borderline, including noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP). Results: Of the 114 nodules, 32.5% were AUS‐Architectural, 28.9% AUS‐Nuclear and Architectural, 18.4% AUS‐Nuclear, 19.3% AUS‐Hürthle cell, and 0.9% AUS‐Not Otherwise Specified. Papillary carcinoma, predominantly follicular variant, was the most common diagnosis (47.4%), followed by benign lesions (34.2%) and NIFTP (9.6%). RAS family mutations were the most prevalent molecular alteration (34.2%) followed by DICER1 , EIF1AX , EXH1 mutations, CNA and GEP (29.8%). THADA fusions, PTEN , TSHR and BRAFK601E mutations were identified in 10.5% of cases, while high‐risk mutations such as BRAF V600E , TERT , and TP53 were found in 8.8% of cases. AUS subcategories demonstrated distinct molecular profiles and were linked to varying surgical outcomes. Conclusions: AUS subcategorization is associated with specific molecular profiles and surgical outcomes, supporting the subclassification of AUS cases per TBSRTC guidelines for improved risk stratification and clinical management. Further prospective studies with larger cohorts are necessary for validation.

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.

Background/Objectives: Since 2021, indeterminate thyroid nodules have been routinely assessed using molecular testing through Quebec’s provincial ThyroSeq v3 pilot project. The primary objective of our study was to compare the molecular and clinicopathological characteristics of Bethesda III and Bethesda IV thyroid nodules evaluated through the pilot project. The secondary objective was to assess the program’s economic impact. Methods: This retrospective study included 934 patients (mean age 55.7 ± 14.3 years; 79.3% female; mean nodule size 2.2 ± 0.8 cm) from two McGill University teaching hospitals in Quebec, comprising 593 Bethesda III and 341 Bethesda IV nodules that underwent molecular testing between 2021 and 2025. Eligible nodules were TI-RADS 3 or 4, measured 1–4 cm, and Bethesda III nodules required two consecutive cytology results before testing. Clinicopathological characteristics, histopathological diagnoses, molecular findings, and mutational profiles were analyzed. A projected 10-year cost analysis was also performed. Results: Of the 934 nodules tested, 280 demonstrated a genetic alteration. The risk of malignancy among surgically resected ThyroSeq v3-positive Bethesda III and IV nodules was 68% and 78%, respectively. Compared with Bethesda III nodules, Bethesda IV nodules demonstrated significantly greater vascular invasion (p = 0.029) and prevalence of oncocytic carcinomas (p = 0.010). Molecular testing was associated with an estimated reduction of 1.49 million Canadian dollars in healthcare costs over 10 years. Conclusions: Although Bethesda IV nodules exhibited more oncocytic carcinomas and invasion, molecular mutation class distribution and the prevalence of aggressive pathological features were similar between Bethesda categories. Together with the demonstrated economic savings, these findings support continued implementation of publicly funded ThyroSeq v3 testing to improve management of indeterminate thyroid nodules while reducing unnecessary surgery.

Introduction: Cancer cachexia is characterized by skeletal muscle loss, poor nutrition, and systemic inflammation and is common in head and neck cancer. We evaluated whether the Cachexia Index (CXI) predicts treatment toxicity and survival in HPV‐negative HNSCC. Methods: This study included 353 patients undergoing curative‐intent surgery at two McGill University hospitals (2015–2025). Pretreatment CXI was calculated using skeletal muscle index, serum albumin, and neutrophil‐to‐lymphocyte ratio. Multivariable logistic and Cox regression assessed associations with severe treatment toxicity (CTCAE grade ≥ 3), overall survival (OS), and disease‐free survival. Results: The lowest CXI quintile was independently associated with severe treatment toxicity (OR 2.04, 95% CI 1.07–3.87). The two lowest CXI quintiles were associated with worse OS (HR 3.00 and 2.83), while each 100‐unit CXI increase reduced mortality risk by 8.9% (HR 0.91, 95% CI 0.86–0.97). Conclusions: Low pretreatment CXI was independently associated with severe treatment toxicity and poorer overall survival. However, CXI was not independently associated with treatment intolerance or disease‐free survival after multivariable adjustment. These findings support further evaluation of CXI as a pretreatment risk stratification tool.

Background: Drooling is a prevalent and disabling condition leading to serious psychosocial and health ramifications. The aim of this study is to analyze the efficacy and safety of 4- versus 2-duct ligation in treating anterior drooling. Methods: A systematic review of the CINAHL, PubMed, and Embase databases was conducted from inception to September 13, 2025. Inclusion criteria were the analysis of both the success rate and associated complications of 2-duct ligation or 4-duct ligation as an independent treatment strategy for anterior drooling. Results: 4-duct ligation showed a higher success rate risk difference (RD) 0.47 (95% CI [0.25, 0.68]), risk ratio (RR) 2.99 ([2.15, 4.15]) than 2-duct ligation with a comparable or lower complication rate. Reported complications included ranula, infection, bleeding, dryness, pain and swelling, anesthesia complications, and others. The most common complication seen in both types of duct ligation was infection. Conclusion: Ductal ligation serves as a safe and effective surgical treatment option for patients with anterior drooling. The high success rate, low operative morbidity, and non-invasive nature of the procedure make it a favorable intervention. Due to the small and variable sample sizes of each intervention, an accurate comparison for efficacy and safety cannot be made between 2- and 4-duct ligations.

Background/Objectives: Since 2021, indeterminate thyroid nodules have been routinely assessed using molecular testing through Quebec’s provincial ThyroSeq v3 pilot project. The primary objective of our study was to compare the molecular and clinicopathological characteristics of Bethesda III and Bethesda IV thyroid nodules evaluated through the pilot project. The secondary objective was to assess the program’s economic impact. Methods: This retrospective study included 934 patients from two McGill University teaching hospitals in Quebec, comprising 593 Bethesda III and 341 Bethesda IV nodules that underwent molecular testing between 2021 and 2025. Eligible nodules were TI-RADS 3 or 4, measured 1–4 cm, and Bethesda III nodules required two consecutive cytology results before testing. Clinicopathological characteristics, histopathological diagnoses, molecular findings, and mutational profiles were analyzed. A projected 10-year cost analysis was also performed. Results: Of the 934 nodules tested, 280 demonstrated a genetic alteration. The risk of malignancy among surgically resected ThyroSeq v3-positive Bethesda III and IV nodules was 68% and 78%, respectively. Bethesda IV nodules demonstrated significantly greater vascular invasion (p = 0.029) and prevalence of oncocytic carcinomas (p = 0.010). Molecular testing was associated with an estimated CAD 1.49 million reduction in healthcare costs over 10 years. Conclusions: Although Bethesda IV nodules exhibited more oncocytic carcinomas and invasion, molecular mutation class distribution and the prevalence of aggressive pathological features were similar between Bethesda categories. Together with the demonstrated economic savings, these findings support continued implementation of publicly funded ThyroSeq v3 testing to improve management of indeterminate thyroid nodules while reducing unnecessary surgery.