In the past few decades, molecular characterization of thyroid cancer has made significant progress and is able to identify thyroid-cancer-related molecular markers that can then be applied clinically for improved decision making. The aim of this review is to provide a general overview about the molecular markers (mutations and alterations) of thyroid cancers, present several molecular tests, and discuss the clinical applications of identifying these markers supported by the clinical experience of several high-volume thyroid cancer specialists at the McGill university hospitals in Montreal, Canada. Our group experience showed that molecular testing can reclassify more than half of the patients with indeterminate thyroid nodules (Bethesda III and IV) into benign and spare these patients from unnecessary diagnostic surgery. Furthermore, it can help optimize the initial management in thyroid cancers with no evidence of high risk of recurrence of disease preoperatively. While routine molecular testing is not firmly established for thyroid FNA specimens that are suspicious or positive for malignancy (Bethesda V and VI), knowledge of a thyroid nodule’s molecular risk group profile in such cases, together with its clinical and radiologic features, can help select the optimal surgical options (lobectomy versus upfront total thyroidectomy and central neck dissection), as demonstrated by our studies.

While some studies suggest that PTEN mutations correlate with a low-risk phenotype in pediatric thyroid nodules, the relationship between the mutation and malignancy in the adult populations is abstruse. This study investigated whether PTEN mutations result in thyroid malignancy, and whether these malignancies are aggressive. This multicenter study involved 316 patients who underwent preoperative molecular testing, and subsequent lobectomy or total thyroidectomy at two quaternary care hospitals. A four-year retrospective review was performed on the 16 charts of patients that opted for surgery following a positive PTEN mutation on molecular testing results from January 2018 to December 2021. Of the total 16 patients, 37.5% (n = 6) had malignant tumours, 18.75% (n = 3) had non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), and 43.75% (n = 7) had benign disease. Aggressive features were detected in 33.33% of the malignant tumours. Malignant tumours were found to have a statistically significant higher allele frequency (AF). The aggressive nodules were all poorly differentiated thyroid carcinomas (PDTCs) with copy number alterations (CNAs) and the highest AFs.

Background: A BRAF V600E mutation in papillary thyroid cancer (PTC) has been shown to be associated with aggressive behavior. Nevertheless, not all BRAF V600E PTCs behave aggressively. Allele frequency (AF) is the number of mutated molecules divided by the total number of wild-type molecules at a specific location in the genome. The relationship between BRAF V600E AF and the histopathological features of thyroid malignancies is not well understood. We hypothesized that the BRAF V600E AF will correlate directly with aggressive histopathological behavior. The aim of this study was to examine this relationship. Methods: A retrospective chart review was performed for patients treated for BRAF V600E thyroid malignancies from 2019 to 2022 at McGill University tertiary care hospitals (n = 317). Patients with BRAF V600E-positive malignancies that included information on AF were included (n = 44). The correlation between AF and tumor histopathological features was analyzed. Results: Out of the 44 nodules with a BRAF V600E mutation, those with aggressive features of PTC had a mean AF of 25.8%, which was significantly higher than the non-aggressive group with a mean AF of 10.25% (p = 0.020). Additionally, there was a statistically significant difference in mean AF between patients with a positive sentinel LN (29%) and those with a negative sentinel LN (17.8%) (p = 0.021). Classical PTC was present in 29.5% (13/44) of nodules, with a mean AF of 15.6%. The tall cell subtype was found in 64% (28/44) of nodules, with a mean AF of 23%. Solid and hobnail subtypes were less common in this study, and there was no statistically significant relationship between AF and histopathological subtypes (p = 0.107). Nodules smaller than 1cm had a mean AF of 13.3%, while nodules ranging from 1 2cm had a mean AF of 20.6%, and those larger than 2cm had a mean AF of 27.7%. However, no statistical difference was observed between AF and nodule size (p = 0.160). Conclusion: In this study, BRAF V600E mutations in conjunction with AF help to determine whether thyroid malignancies will display aggressive behavior. This pre-operative finding can help thyroid specialists to determine the extent of thyroidectomy and whether lymph node dissection is required.

Septorhinoplasty is a surgical procedure that provides functional improvements and esthetic adjustments to the appearance of the nose. Pain is a common postoperative complication, and pain management is known to decrease postoperative complications and total cost. Local anesthetics can cost-effectively decrease postoperative pain scores and reduce analgesic requirements. The primary objective of this study was to assess the effect of bilateral facial nerve blocks given with general anesthesia on pain scores and the use of postoperative analgesia. The secondary objective was to compare the vital signs stability between a group given bilateral facial nerve blocks with general anesthesia and a group given general anesthesia only. We conducted a retrospective observational study among 40 patients who were divided into two groups, each containing 20 patients. The patients in the nerve block (NB) group received general anesthesia and bilateral facial blocks of the infraorbital and infratrochlear nerves via 5 ml of 0.25% levobupivacaine with 5 ml of diluted adrenaline 1:100,000. Patients in the Control group received general anesthesia only. Both groups received the same local injection of a mixture of 5 ml of 1% lidocaine and 5 ml of 1:100,000 epinephrine at the surgical site, along with the standard general anesthesia. A numerical rating scale, the visual analog scale (VAS), was used to evaluate postoperative pain at 15, 30, and 45 minutes postoperatively, and the stability of the vital signs was also assessed. The results showed that using bilateral infraorbital and infratrochlear nerve block injection with 0.25% levobupivacaine for patients who underwent septorhinoplasty under general anesthesia provided greater stability of vital signs but had no effect on the pain score or analgesia need. Further assessment should be performed in a larger number of patients to either confirm or refute these results. Additional studies could be conducted in several hospitals within the Kingdom to determine how broadly applicable nerve blockade is in reducing pain sensation.

The diagnosis of craniofacial osteosarcoma can be quite challenging, and the condition often goes unrecognized for a considerable period of time. In this report, we discuss the case of a 21-year old woman who presented with a one-year history of a small swelling over the left maxillary alveolar ridge. Upon further investigation, the histopathological examination showed high-grade chondroblastic osteosarcoma. The option of four cycles of neoadjuvant chemotherapy regimen preoperatively was chosen, and left inferior maxillectomy was performed along with reconstruction with obturator prosthesis. This case highlights the difficulties encountered in such rare cases of craniofacial osteosarcomas both in terms of the delay in the establishment of the diagnosis as well as management protocol. A high index of suspicion is required in cases of craniofacial osteosarcoma and early surgical resection with adequate safety margins is warranted.

ThyroSeq V3 (TsV3) tests for various genetic alterations, including gene expression alterations (GEAs), to improve diagnostic accuracy and clinical decision-making for indeterminate thyroid nodules. This study aimed to clarify the clinico-pathological features and outcomes of GEA-positive thyroid nodules, which have not yet been well-described in the literature. A retrospective chart review was performed whereby patients were included if they underwent thyroid surgery between January 2018 and May 2022 at two McGill University teaching hospitals and their surgery was preceded by pre-operative molecular TsV3 testing. In total, 75 of the 328 patients with thyroid nodules (22.9%) who underwent molecular testing and surgery were GEA-positive. On surgical pathology, GEA-positive nodules showed a significantly higher malignancy rate compared to their GEA-negative counterparts (90.7% vs. 77.7%, respectively, p = 0.011). Among those that were malignant, 48.5% had at least one aggressive pathological feature, including histological subtype, extra-thyroidal extension, or lymph node metastasis. BRAF V600E mutation had a significantly greater association with aggressive malignant GEA-positive nodules compared to non-aggressive ones (p < 0.001). This study demonstrates that GEA may be an effective diagnostic and prognostic tool for thyroid nodule management. However, further investigation is needed to characterize the clinico-pathological features of GEA in isolation and in association with other gene alterations.