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Background: Molecular testing can reduce the need for diagnostic thyroidectomy in cytologically indeterminate thyroid nodules. However, the health-related quality of life in patients managed with molecular testing is not well studied. Objective: The objective of this scoping review was to identify and analyze the health-related quality of life outcomes in patients with indeterminate thyroid nodules who are expected to undergo or have undergone surgery or molecular testing. Methods: A comprehensive search was conducted on PubMed, Scopus, PsychINFO, and Embase to identify relevant studies. The search terms included "thyroid neoplasms" or "thyroid nodule" and "molecular testing" or "surgery" and "quality of life". The included articles were analyzed for their main study objective, study design, participant characteristics, and main results. Results: Eight studies were included in this scoping review. Four evaluated the quality-adjusted life years for patients with indeterminate thyroid nodules. Three of these studies found that molecular testing slightly improved quality-adjusted life years compared to surgery, while one study found no difference. Two studies assessed surgical health-related quality of life outcomes and reported that patients with indeterminate thyroid nodules who were expected to undergo surgery favored surgical procedures, while those who underwent surgery experienced impaired health-related quality of life. Two studies evaluated molecular testing in patients with indeterminate thyroid nodules and found that the final molecular test result significantly impacted health-related quality of life outcomes. Patients with suspicious/positive molecular test results had worse symptoms of goiter, anxiety, and depression, while those with benign results had preserved health-related quality of life scores. Patients with benign results from molecular testing experience better health-related quality of life within the first year compared to those with benign surgical outcomes. Conclusions: This scoping review highlights the importance of considering health-related quality of life outcomes in the management of patients with indeterminate thyroid nodules. Benign molecular testing results yield better quality of life than benign surgical outcomes within the first year, suggesting molecular testing as a preferable option. Further research comparing the impact of surgery and molecular testing on health-related quality of life is needed to improve shared decision-making and patient outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores the impact of telomerase reverse transcriptase (TERTp) molecular alterations on the behavior of thyroid nodules, exploring the differential behavior of these molecular alterations occurring alone versus with concurrent molecular alterations. By analyzing the data from thyroid cancer patients treated between 2017 and 2024, this study aimed to clarify how the genetic landscape of TERTp molecular alterations relates to severity and various clinical and histopathological features of disease. The study found that thyroid cancers harboring both TERTp and concurrent molecular alterations were more likely to be classified as high-risk and have aggressive histology in contrast to nodules with TERTp molecular alterations in isolation, which generally showed less aggressive behavior. These findings suggest that identifying concurrent molecular alterations in TERTp-positive thyroid nodules could improve cancer risk assessment and prognosis and inform more tailored treatment strategies. 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. [ABSTRACT FROM AUTHOR]

Background: Oncocytic thyroid carcinoma (OTC) was previously considered a variant of follicular thyroid carcinoma (FTC) but has recently been reclassified as a separate form of thyroid cancer. This study aimed to demonstrate that FTC and OTC are fundamentally distinct entities that can potentially be differentiated preoperatively through cytology and/or molecular testing. Methods: A retrospective chart review of patients diagnosed with FTC and OTC operated upon at two university health centers from January 2016 to September 2023 (n = 3219) was conducted. Molecular testing results were correlated with histopathologic diagnosis. Results: Fifty patients met the inclusion criteria. FTC was identified in 27 (54.0%) patients, and OTC in 23 (46.0%) patients. Patients with OTC were older (61.8 years) than FTC patients (51.2 years) (p = 0.013). Moreover, aggressive tumors were found in 39.1% (9/23) of OTCs compared to 11.1% (3/27) of FTCs (p = 0.021). Amongst Bethesda category III and IV nodules, 17 out of 20 (85.0%) OTC cytology reports demonstrated an oncocytic subtype compared to only 5 out of 24 FTC cytology reports (20.8%) (p = 0.002). On molecular testing, the EIF1AX alteration was exclusively present in OTCs while the PAX8/PPARy and PTEN alterations were exclusively found in FTCs. Copy number alterations (CNAs) were found to be more prevalent in OTC (66.7%) compared to FTC (33.3%), and they were not indicative of tumor aggressiveness. Within the OTC group, all three patients who had a TP53 alteration were diagnosed with aggressive cancer. Lastly, the OTCs exhibited a higher frequency of multiple alterations on molecular testing (66.7%) compared to FTCs (33.3%). Conclusion: To our knowledge, this is the largest study to date comparing the clinical application of abnormalities found on molecular testing for FTC and OTC. It further demonstrates the distinct clinicopathological and molecular characteristics of OTC. [ABSTRACT FROM AUTHOR]

Background: Ki-67 immunostaining is commonly used in neuroendocrine tumors to estimate the proliferative index and for grading. This study investigates its association with the invasiveness of follicular-derived thyroid carcinomas (TCs). Methods: A retrospective analysis of patients with TC at three McGill University teaching hospitals between January 2018 and November 2023 was conducted. The inclusion criteria included patients with malignant thyroid tumors and accessible Ki-67 LI data from final pathology specimens. The data collected included patient demographics, Ki-67 LI values, and different invasiveness attributes, such as molecular mutations, the histological subtype, lymphovascular invasion (LVI), extrathyroidal extension (ETE), and positive lymph nodes (LNs). Results: In total, 212 patients met the inclusion criteria, of which 80.7% were females and 19.3% were males. The Ki-67 LI ranged from 1% to 30%, with the majority of the cases within the range of 1–15%. A significant association was observed between higher Ki-67 LI and high-risk histological subtypes of thyroid carcinoma (p < 0.001). Similarly, Ki-67 LI was significantly associated with LVI and positive LN metastasis (p < 0.001 and p = 0.036, respectively). However, no significant association was found between the Ki-67 LI and gene mutations or ETE (p = 0.133 and p = 0.190, respectively). Using percentiles to establish a cutoff, patients with a Ki-67 LI higher than 6.7 showed a higher likelihood of being associated with invasive features. Conclusion: Elevated Ki-67 LI can serve as an indicator of aggressiveness in follicular-derived TC, especially when associated with distinct histological subtypes, LVI and positive LNs. [ABSTRACT FROM AUTHOR]

Background: While ultrasound-guided fine-needle aspiration cell block (FNACB) is a cost-effective, expeditious, and reliable procedure used routinely in the initial evaluation of head and neck masses, it has limited efficacy in diagnosing lymphoproliferative disorders such as non-Hodgkin lymphoma (NHL). Flow cytometry performed on an fine-needle aspiration (FNA) sample [ultrasound-guided fine-needle aspirate flow cytometry or flow cytometry performed on an FNA sample (FNAFC)], has been shown to be a valuable adjunct to FNACB in the diagnosis of lymphoproliferative disorders of the spleen, kidney, and thyroid. The objective of this study was to appraise FNAFC's utility as an ancillary tool to detect NHL arising in the head and neck region in adult patients. Methods: This is a retrospective study involving 52 adult patients with head and neck lymphadenopathies and masses suspicious for lymphoproliferative disorders, who underwent ultrasound-guided FNACB and ultrasound-guided FNAFC between January 2017 and November 2022. Patient demographics, FNACB histopathological and immunophenotypic results, postoperative histopathology results (when available), and follow-up information until May 2023 were reviewed. Results: Of the 52 FNACB samples, 23 samples (44.2%) yielded a diagnosis negative for carcinoma, 20 samples (38.5%) were nondiagnostic on account of scant cellularity, 8 samples (15.4%) were suspicious for malignancy, and a single sample (1.9%) was compatible with malignancy. Regarding FNAFC samples, 37 samples (71.2%) were diagnosed as showing no evidence for a lymphoproliferative disorder, 4 samples (7.7%) as nondiagnostic because of insufficient cell count, 4 samples (7.7%) as suspicious for a lymphoproliferative neoplasm, and 7 samples (13.5%) as compatible with a lymphoproliferative neoplasm, most frequently a B-cell lymphoma. 7 of the 11 patients (63.6%) with a suspicious/positive FNAFC result underwent excisional biopsy for additional work up. Postoperative histopathology reports corroborated FNAFC's findings in 6 patients (85.7%), while the remaining patient's (14.3%) suspicious FNAFC result was discordant with postoperative histopathology results. The other 4 patients (36.4%) did not require excisional biopsy as the hemato-oncologist deemed the information provided by the FNAFC as sufficient for the diagnosis and treatment of an NHL in the specific clinical contexts of those patients. All patients with nondiagnostic (due to insufficient cell count), inconclusive, or negative FNAFC (ie, nondiagnostic of a lymphoproliferative disorder) were followed up for a mean follow-up period of 11.9 months (range: 61.2 months; SD: 10.2 months), during which no new lymphadenopathies/masses nor progression was observed. Conclusions: FNAFC is a useful and practical supplementary tool in the diagnosis of lymphoproliferative disorders in the head and neck region, principally B-cell lymphoma. While conventional FNACB offers a valuable insight into the initial work up of head and neck masses, FNAFC can routinely detect small abnormal cell populations. Furthermore, in specific clinical contexts, it can reliably diagnose NHL, thereby averting the need for an excisional biopsy in a subset of patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to investigate the relationship between the allele frequency (AF) of the BRAF V600E mutation and the histopathological features of papillary thyroid cancer (PTC), with a focus on its aggressive behavior. The research involved a retrospective chart review of 44 patients with BRAF V600E-positive thyroid malignancies, and the results indicated a direct correlation between BRAF V600E AF and aggressive histopathological behavior. Specifically, nodules with aggressive PTC features exhibited a significantly higher mean AF (25.8%) compared to the non-aggressive group (10.25%). Additionally, a significant difference in mean AF was observed between patients with positive sentinel lymph nodes (29%) and those with negative sentinel lymph nodes (17.8%). Although different histopathological subtypes showed varying mean AF values, they did not exhibit a statistically significant relationship. The study findings suggest that the BRAF V600E mutation, in combination with AF, can serve as a pre-operative indicator to help thyroid specialists determine the extent of thyroidectomy and the necessity of lymph node dissection, providing valuable insights for the management of thyroid malignancies in clinical practice. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Around 25% of patients who undergo an ultrasound-guided thyroid biopsy end up with an indeterminate result based on cytology. This has propelled the use of other modalities, such as molecular testing, to further stratify these patients. The aim of our retrospective study was to report and compare two genetic mutations in our patient population. These mutations are RET/PTC and THADA/IGF2BP3 translocations, which have been hypothesized as oncogenic events in thyroid neoplasms. We confirm that our patient population exhibited these mutations, and all underwent a final histopathology analysis where surgery was the preferred treatment modality. We also report that the RET/PTC fusion exhibited more aggressive features than the THADA/IGF2BP3 fusion and was more likely to need post-surgical treatment. Background: Molecular testing has been used as an adjunct to morphological evaluation in the workup of thyroid nodules. This study investigated the impact of two gene fusions, RET/PTC and THADA/IGF2BP3, that have been described as oncogenic events in thyroid neoplasms. Methods: We performed a retrospective, single-centered study at a McGill University teaching hospital in Montreal, Canada, from January 2016 to August 2021. We included patients who underwent surgery for thyroid nodules that pre-operatively underwent molecular testing showing either RET/PTC or THADA/IGF2BP3 gene fusion. Results: This study included 697 consecutive operated thyroid nodules assessed using molecular testing, of which five had the RET/PTC fusion and seven had the THADA/IGF2BP3 fusion. Of the five nodules in the RET/PTC group, 100% were malignant and presented as Bethesda V/VI. Eighty percent (4/5) were found to have lymph node metastasis. Twenty percent (1/5) had extrathyroidal extensions. Sixty percent (3/5) were a diffuse sclerosing variant of papillary thyroid carcinoma, and the rest were the classical variant. Of the seven THADA/IGF2BP3 nodules, all presented as Bethesda III/IV and 71.4% (5/7) were malignant based on the final pathology analysis, and 28.6% (2/7) were NIFTP. All the THADA/IGF2BP3 fusion malignancies were a follicular variant of papillary thyroid carcinoma. None had lymph node metastasis or displayed extrathyroidal extensions. Conclusions: RET/PTC nodules presented as Bethesda V/VI and potentially had more aggressive features, whereas THADA/IGF2BP3 nodules presented as Bethesda III/IV and had more indolent behavior. This understanding may allow clinicians to develop more targeted treatment plans, such as the extent of surgery and adjuvant radioactive iodine treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: PTEN mutation is an extremely rare mutation in thyroid nodules with no clear prognostic indicators. In this multicenter study of 16 PTEN-mutated thyroid nodules, we found that 37.5% of the nodules were malignant. Aggressive features were present in 33.33% of the malignant tumours. We hypothesize that with time, PTEN-mutated thyroid nodules can acquire high allele frequencies (AFs) and widespread copy number alterations (CNAs), which might be aggravating the effects of PTEN mutations. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: As molecular testing of thyroid nodules becomes more common, thyroid specialists must be able to interpret and understand the clinical implications of the results. A telomerase reverse transcriptase (TERT) promoter mutation can strongly predict thyroid cancer aggressiveness. However, the reason why some thyroid cancers with TERT promoter mutations are more aggressive than others remains unclear. This study aimed to examine whether TERT promoter mutations coexisting with other mutations are linked to more aggressive disease than TERT promoter mutations alone. The medical records of patients who had thyroid surgery and TERT promotor mutations were examined. Our findings showed that the likelihood of aggressive thyroid cancers was 10 times higher in patients with TERT promoter and other concurrent mutations. Thyroid specialists can use our results to accurately interpret the molecular testing of thyroid nodules, provide appropriate counseling, and discuss possible management options accordingly. This study aimed to examine whether concurrent mutations with a TERT promoter mutation are associated with a greater likelihood of more aggressive disease than a TERT promoter mutation alone. The medical records of 1477 patients who underwent thyroid surgery at two tertiary hospitals between 2017 and 2022 were reviewed. Twenty-four patients had TERT promoter mutations based on molecular profile testing. Clinicodemographic data, mutational profiles, and histopathological features were assessed. Descriptive analysis, Fisher's exact test, and binary logistic regression were performed. Seven patients had single-gene TERT promoter mutations, and 17 had concurrent mutations, including BRAF V600E, HRAS, NRAS, PIK3CA, and EIF1AX. The overall prevalence of malignancy was 95.8%, of which 78.3% were aggressive thyroid cancers. There was a statistically significant association between concurrent mutations and disease aggressiveness. The odds of having aggressive disease were 10 times higher in patients with a TERT promoter mutation and a concurrent molecular alteration than in those with a TERT promoter mutation alone. This is an important finding for thyroid specialists to consider when counseling patients concerning risk stratification and management options. [ABSTRACT FROM AUTHOR]

Simple Summary: Copy number alterations are known to be present in some thyroid tumors; however, their idiosyncratic clinicopathological implications are not yet well elucidated. In this study we reviewed 67 thyroid nodules with positive copy number alterations who underwent surgery. We discovered that most of the thyroid nodules with positive copy number alterations were malignant or non-invasive follicular thyroid neoplasm with papillary-like nuclear features and the presence of coexisting molecular alterations increased the risk of malignancy in these nodules. These findings may affect the decision-making in individuals with copy number alterations positive thyroid nodules. Molecular mutations and alterations play a role in thyroid tumorigenesis. Different alterations are associated with different clinical and pathological characteristics. Copy number alterations (CNAs) are known to be present in some thyroid tumors; however, their idiosyncratic clinicopathological implications are not yet well elucidated. A retrospective chart review was performed to identify patients with CNAs on pre-operative molecular testing results who subsequently underwent surgical treatment between January 2016 and April 2022 at McGill University teaching hospitals. Of the 316 patients with thyroid nodules who opted for molecular testing with ThyroSeqV3 followed by surgery, 67 (21.2%) nodules were positive for CNAs, including 23 Bethesda III, 31 Bethesda IV, 12 Bethesda V and 1 Bethesda VI nodules. On surgical pathology, 29.9% were benign and 70.1% were malignant or non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Among those that were malignant/NIFTP, 17.02% were considered to be aggressive cancers. The presence of other molecular alterations was found to be an independent predictor of malignancy in multivariate analysis (OR = 5.087, 95% C.I. = 1.12–23.04, p = 0.035). No unique factor was correlated with aggressiveness; however, CNA-positive thyroid nodules that were associated with high-risk mutations such as BRAF V600E, TP53, NTRK1/3 fusion, or PTEN mutation with high allele frequency (AF) ended up being aggressive cancers. Most of the CNA-positive thyroid nodules resulted in follicular patterned tumors in 41 (65.2%) cases and oncocytic tumors in 20 (29.9%) cases. This study demonstrates that 70.1% of surgically resected thyroid nodules with CNAs were malignant/NIFTP. Most CNA-positive thyroid nodules were either oncocytic patterned tumors or follicular patterned tumors. Furthermore, CNA-positive thyroid nodules were more likely to be malignant if they were associated with other molecular alterations or mutations. [ABSTRACT FROM AUTHOR]

Simple Summary: Ultrasound-guided fine-needle aspiration (USFNA) biopsy is a widely used first-line diagnostic approach to differentiate between benign and malignant tumors. However, 15–30% of all thyroid nodules investigated by USFNA cytology are indeterminate. To address the elusive clinical management of such nodules, molecular markers for common mutations in thyroid cancer have been researched to serve as prognostic indicators. EIF1AX is a rare mutation with no clear prognostic indicators. In this multicenter study of 42 EIF1AX-mutated thyroid nodules, we found that 47.6% of nodules were malignant with distinctive risks of malignancy depending on the location of the mutation and the presence of co-mutation(s). An EIF1AX A113_splice site mutation in tandem with a RAS and/or TP53 mutation is associated with aggressive malignancies that have an inherent potential to progress toward poorly differentiated thyroid carcinoma. The risk of malignancy (ROM) of EIF1AX-mutated thyroid nodules has been theorized to be contingent on the position of the mutation within the gene and the presence of co-existing mutations. However, due to EIF1AX's low mutation frequency, sample sizes currently reported in the literature are too diminutive to appraise the clinical utility of molecular diagnostic testing. The objective of this study was to elucidate prognostic indicators of EIF1AX-mutated thyroid tumors and cancer aggressiveness by examining a large cohort of cytologically indeterminate thyroid nodules (CITNs) that underwent molecular testing and subsequent surgical resection. This is a multicenter study involving 764 subtotal and total thyroidectomy patients that underwent preoperative molecular testing at two quaternary care hospitals. A five-year retrospective review was performed on the 42 charts of patients that opted for surgery following a positive EIF1AX mutation on ThyroseqV3 results from January 2018 to May 2022. Patient demographics, cytopathology results, molecular testing results, and postoperative histopathology were reviewed. Of the 42 surgically resected nodules that harbored an EIF1AX mutation, 16 (38.1%) were benign, six (14.3%) were non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) or well-differentiated thyroid neoplasms of uncertain malignant potential (WDT-UMPs), and 20 (47.6%) were malignant. An isolated EIF1AX mutation conferred a ROM of 47.6%, whereas the ROM for nodules with at least one additional molecular alteration was 72.7%. The ROM increased to 100% for nodules with at least one additional molecular alteration and the A113_splice site mutation. Six malignant nodules were aggressive, with five having variegated components of poorly differentiated thyroid carcinoma (PDTC). EIF1AX-mutated thyroid nodules are more susceptible to malignancy in the presence of the A113_splice site mutation and when co-mutated with RAS and/or TP53. This deleterious amalgam is associated with aggressive disease and renders these nodules PDTC. A preoperative molecular test finding of an EIF1AX mutation can be a useful tool for thyroid specialists to optimize clinical management. [ABSTRACT FROM AUTHOR]

Simple Summary: 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 teaching hospitals in Montreal, Canada. 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. [ABSTRACT FROM AUTHOR]

Patients with head and neck cancer report high unmet psychosocial needs as they undergo lifesaving treatments that can significantly alter their appearance and cause functional impairments. This qualitative analysis of recordings of 88 pre- and post-surgical consultations involving 20 patients respond to the need for empirical studies of patient–provider conversations about body image concerns. It indicates that the emphasis on concerns about survival, cure, and physical recovery during clinical consultations may leave concerns about the impacts of surgery on appearance and function unexplored and even silenced. The interviews with patients and medical team members that complement the analysis of the recordings suggest that an emphasis on survival, cure, and physical recovery can respond to the need for reassurance in the context of serious illness. However, it can also be problematic as it contributes to the silencing of patients' concerns and to a potential lack of preparedness for the consequences of surgery. The results of this study can contribute to raising surgeons' awareness of the interactional dynamics during clinical consultations. Moreover, the results highlight the unique role that surgeons can play in validating patients' psychosocial concerns to support patients' rehabilitation in both physical and psychosocial domains. [ABSTRACT FROM AUTHOR]

Background: Although the current gold standard for diagnosing thyroid nodule malignancy is ultrasound-guided fine-needle aspiration (FNA) cytology, about 20–25% of cytological evaluations are considered indeterminate for malignancy. This limitation has led to the emergence of next-generation sequencing panels, for example, ThyroSeq v3 (TSv3), which recognize highly diagnostic genetic mutations of common thyroid carcinomas in FNA samples and classify them as test-negative or test-positive, helping optimize treatment for indeterminate thyroid nodules (ITNs). Our goals were to evaluate the benign call rate (BCR) of TSv3 and assess its diagnostic performance and clinical utility while highlighting the points of consideration for a public Canadian institution. Methods: This is a single-center study conducted at the Royal Victoria Hospital (McGill University Health Centre) in Montreal, Canada, between January and February 2019. Patients were offered TSv3 following the McGill algorithm for ITN workup, a novel protocol developed at our institution to select only diagnostic surgery candidates to minimize waste of public resources, considering the single-payer health care system. Patient demographics, cytopathology results, TSv3 data, treatment plan, and final histopathology result were reviewed. Results: A total of 50 ITNs underwent TSv3 testing; molecular analysis yielded 20 (40%) "positive" results and 24 (48%) "negative" results. Six (12%) results were classified as "currently negative" or "negative but limited." "Currently negative" results indicate a low-risk mutation that alone is insufficient for development of a malignant lesion. "Negative but limited" results indicate a sample that is nondiagnostic for malignancy due to low cell count. BCR was calculated as ("negative" and "currently negative")/total, resulting in a BCR of 58%. Twenty-three (46%) patients were scheduled for surgery and 27 (54%) patients continued with surveillance. Ninety-one percent (20 of 22) of the resected target nodules were malignant on final pathology. Conclusions: TSv3 proved beneficial in classifying ITNs as positive or negative, avoiding surgery in the latter cases. We found a lower reduction rate in surgery and BCR than the previously published studies, which is attributable to the criteria of the McGill algorithm. In the Canadian public health care system, preventing unnecessary surgery represents significant cost savings for the provincial government while also improving patient quality of life. [ABSTRACT FROM AUTHOR]

Background: Management decisions are not straightforward when the Ultrasound Guided Fine Needle Aspiration (USFNA) demonstrates a Bethesda score of either category III or IV, and a diagnostic hemi-thyroidectomy or a repeat USFNA (r-USFNA) could be performed. The aim of this study is to assess the effectiveness of r-USFNA in the management of indeterminate thyroid nodules by evaluating the likelihood of obtaining a definite diagnosis. Methods: We reviewed the medical records of all patients with thyroid nodules between 2011 and 2015 at the Jewish General Hospital (Montreal, Canada). Three hundred fifty-one patients who had undergone a surgical procedure (hemi or total thyroidectomy) and a diagnosis of B3 or B4 on the primary USFNA (p-USFNA) were included in the study. Ninety-six of the included patients also had a repeat USFNA prior to the surgery. Demographic data, type of procedure, and McGill Thyroid Nodule Score (MTNS) were obtained from the medical records. Malignancy rates were calculated based on the final surgical histopathology report. Results: Upon r-USFNA, an average 76 % of patients did not change Bethesda categories, 7.4 % downgraded to a benign category. The results showed that, on an average 17.3 % of patients with p-USFNA of B3 and 20 % of patients with p-USFNA of B4, upgraded to a malignant or suspicious for malignancy category, thus changing the clinical management to total thyroidectomy. Our data demonstrates that r-USFNA facilitates choosing the correct surgery of total thyroidectomy in about 20 % of nodules that have upgraded from B3/B4 to a more definite malignant category. Conclusions: r-USFNA in patients with indeterminate diagnoses (B3 or B4) increases categorization into more definite categories. Approximately 20 % of patients are found to have malignant thyroid nodules and suspicious for malignancy thyroid nodules upon repeating the biopsy, hence a diagnostic hemi-thyroidectomy was avoided and a more definitive surgery could be performed. Furthermore, repeat USFNA results in a fewer number of hemi-thyroidectomy and completion thyroidectomy procedures. [ABSTRACT FROM AUTHOR]

Objective: Hypocalcemia following thyroidectomy often prolongs hospital stay and is potentially life-threatening. The objective of this study is to determine whether the season when thyroidectomy is performed is associated with postoperative hypocalcemia.Study Design: Retrospective case series of patients undergoing thyroid surgery from 2009 to 2015.Setting: Tertiary care academic institution in Montreal, Canada.Subjects and Methods: A consecutive sample of 823 patients undergoing thyroidectomy by a single high-volume otolaryngologist for a suspected or confirmed thyroid malignancy. Patient demographics, procedure type, calcium and vitamin D supplementation, and seasonal rate of hypocalcemia postthyroidectomy were calculated and compared.Results: Average seasonal rates of postthyroidectomy hypocalcemia in the winter, spring, summer, and autumn were, respectively, 8.3% (8 of 216), 7.3% (12 of 165), 1.5% (3 of 201), and 3.5% (8 of 228; P < .005). Patients operated in the winter were 5.6 times more likely to develop hypocalcemia as compared with those in the summer (P < .01; 95% confidence interval: 1.7-18.7). In a multiple regression analysis factoring in season when surgery was performed, procedure type, and preoperative vitamin D/calcium supplementation, surgery occurring in the winter predicted a hypocalcemia event (correlation coefficient [SE]: 0.72 [0.024], P = .026; 0.006 [0.025], P = .81; 0.004 [0.019], P = .82, respectively).Conclusion: In this study, patients undergoing thyroidectomy in the winter months were more likely to develop postoperative hypocalcemia when compared with those operated in the summer. Further studies are needed to understand the role of vitamin D in the observed seasonal difference in hypocalcemia rates. [ABSTRACT FROM AUTHOR]

Background: Vocal cord paralysis (VCP) is found in both benign and malignant thyroid disease. This study was performed to determine if the presence of preoperative VCP predicts malignancy. Methods: A retrospective analysis was performed on a cohort of 1923 consecutive patients undergoing thyroid surgery. The incidence of preoperative VCP was recorded. Patient and nodule characteristics were correlated with final pathology. Results: 1.3 % of our cohort was found to have preoperative VCP. Malignant pathology was discovered in 76 % of patients with preoperative VCP. Among these patients, 72 % had a left sided paralysis. 10.5 % of patients with preoperative VCP had perineural invasion (PNI) on final pathology, compared to 1.1 % of patients with normal VC function. Conclusion: Preoperative VCP appears to be a strong, though not an absolute, indicator of malignancy. Most VCP were on the left side. Assessing for preoperative VCP is crucial in all patients who need thyroid surgery, as even benign nodules can be accompanied by preoperative vocal cord paralysis. [ABSTRACT FROM AUTHOR]

Background: We sought to determine the ability of the endoscopic Mueller maneuver (MM) to predict the severity of OSAS based on upper airway (UA) collapse. Methods: This chart review retrospectively analyzed the results of endoscopic Mueller maneuvers examining the UA on 506 patients suspected of having OSAS. There were 3 areas of UA collapse that were evaluated: velopharynx (VP), base of tongue (BOT), and lateral pharyngeal walls (LPW). A sleep study was done after the examination to assess the severity of OSAS based on the apnea-hypopnea index (AHI). Results: A total of 506 patients met criteria for OSAS, with 194 mild cases (5 ≤ AHI < 15), 163 moderate cases (15 ≤ AHI < 30) and 149 severe cases (30 < AHI). At the VP, 30 patients had minimal collapse (mean AHI = 17); 41 patients had moderate VP collapse (mean AHI = 25); 392 patients had severe VP collapse (mean AHI = 27). At the BOT, 144 patients had minimal collapse (mean AHI = 19); 187 patients had moderate BOT collapse (mean AHI = 24); 175 patients had severe BOT collapse (mean AHI = 33). At the LPW, 158 patients had minimal collapse (mean AHI = 20); 109 patients had moderate LPW collapse (mean AHI = 25); 120 patients had severe LPW collapse (mean AHI =33). The correlations found between VP collapse, BOT collapse, and LPW collapse and OSAS severity were: r= 0.069 (95 % CI; -0.022, 0.16), r= 0.26 (95 % CI; 0.18, 0.34) and r= 0.22 (95 % CI; 0.12, 0.31), respectively. Conclusions: In this study, the degree of collapse of the UA at all levels, especially at the BOT and LPW levels, correlate significantly with the severity of OSAS. The Mueller maneuver helped identify patients with severe sleep apnea based on UA collapse. The MM cannot be used to diagnose OSAS, but can be a valuable tool to help the physician estimate the severity of sleep apnea and the urgency to obtain a sleep study. [ABSTRACT FROM AUTHOR]

Introduction: It is not uncommon for patients with indeterminate thyroid nodules to undergo diagnostic hemithyroidectomy. When the final pathology determines that the nodule is in fact malignant, patients require counseling as to the whether a completion thyroidectomy is necessary. Objectives: 1. Determine the incidence of well differentiated thyroid cancer (WDTC) in the contralateral thyroid lobe in patients undergoing completion thyroidectomy. 2. Identify features of the malignant tumor in the initial resection that increase the likelihood of malignancy in the contralateral lobe. Methods: Retrospective chart review of 97 patients who underwent hemithyroidectomy and completion thyroidectomy in a university's teaching hospital network between 2006 and 2012. Pathology reports from both surgeries as well as patient and thyroid nodule characteristics were reviewed. Results: Of the 97 patients, 47 (48 %) had a malignancy in the contralateral lobe. In the contralateral lobe, 42/47 (89 %) of malignancies were papillary microcarcinomas (PMC) and 15/42 (36 %) of the PMC were multifocal. Multifocal malignancies in the initial specimen had a 60 % rate of contralateral malignancy and were found to be a predictor of bilateral disease (p = 0.04) with OR = 2.74 (95 % CI: 1.11 -6.79; p = 0.003) in WDTC and OR = 3.59 (95 % CI:1.35 9.48; p = 0.01) in papillary cancer specifically. There was no statistical significant correlation established for the following variables: presence of positive cervical nodes, extrathyroidal extension, positive resection margins, size and angio-lymphatic invasion. Moreover, there was no statistical correlation between any of the variants of papillary thyroid cancer and bilateral disease, even though most aggressive subtypes were found to be bilateral. Conclusion: In this study, the rate of malignancy in the contralateral lobe was 48 %. Multifocality and presence of an aggressive subtype of papillary thyroid cancer in the initial specimen were found to be more important variables to consider in decision-making regarding completion thyroidectomy than size of the initial tumor alone. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to prospectively review the role of sentinel lymph node (SLN) biopsy in the management of well differentiated thyroid carcinoma (WDTC), and to determine the efficacy of intraoperative frozen section analysis at detecting SLN metastasis and central compartment involvement. Methods: The SLN biopsy protocol using 1% methylene blue was performed in 300 patients undergoing thyroidectomy for WDTC. A limited pretracheal central compartment neck dissection (CCND) was performed on all patients. Lymph nodes staining blue were considered as SLN's. Both frozen and permanent section analyses were performed. Results: SLN's with metastasis were found in 14.3% (43/300) of cases. Of this, 11% (33/300) were positive on intraoperative frozen section analysis. Frozen section results failed in predicting central compartment involvement in 15 cases (5%) whereas central neck compartment involvement was missed in 5 cases (1.7%) when based on permanent section results. On frozen section analysis, the sensitivity, specificity, positive predictive value and negative predictive value (95% CI) of our SLN biopsy technique aiming to remove all disease from the central compartment was 68.8% (53.6-80.9), 100% (98.1-100), 100% (87.0-100) and 94.4% (90.7-96.7) respectively with P < 0.0001. On permanent section analysis, the values were 89.6% (76.6-96.1), 100% (98.1-100), 100% (89.8-100), and 98.1% (95.3-99.3) with P < 0.0001. Conclusion: This data series demonstrates that patients with WDTC have positive SLN's in 14.3% of cases. Moreover, when the SLN's are negative for metastasis on frozen section, the central compartment was disease-free in 94.4% of cases. Finally, this study shows that 23.3% of positive SLN's were false negatives on intraoperative frozen section. According to this data, SLN involvement is an accurate predictor of central compartment metastasis, however surgeons should use caution when relying on intraoperative frozen section to determine whether to perform a CCND. [ABSTRACT FROM AUTHOR]

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Background: Patients with Graves' ophthalmopathy may need surgical treatment to alleviate ophthalmologic complications. The degree of reduction in proptosis following surgical intervention remains difficult to predict. Objectives: To elaborate a human model using cadaver orbits to study surgical management of Graves' ophthalmopathy. To evaluate quantitatively the contribution of each orbital wall decompression and their combinations in reduction in proptosis. To improve the ability to predict the degree of proptosis reduction according to the wall(s) chosen for decompression. Methods: Artificial exophthalmos was created in 12 cadavers' orbits by injecting a polysaccharide gel in the peribulbar and retrobulbar tissues. Proptosis reduction was measured following successive orbital decompression. Results: Decompression of one wall produced a nonstatistical significant reduction in proptosis. The combination of the medial and lateral walls significantly reduced the proptosis by a mean of 4.2 mm. Three-wall decompression gave a mean significant reduction of 6.6 mm, and when combined with the advancement of the lateral wall, it reduced proptosis by 12.5 mm. Conclusions: We created an experimental model for research and didactic purposes for surgical management of Graves' ophthalmopathy. With this model, to obtain 5 mm or more of proptosis reduction, three-wall decompression is required. Advancement of the later at wall achieved a further reduction in proptosis. For a proptosis reduction of less than .5 mm, decompression of the medial and lateral walls is appropriate. [ABSTRACT FROM AUTHOR]