Characteristics of PTEN Mutation in Thyroid Tumours: A Retrospective Chart Review.

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.

Effect of Having Concurrent Mutations on the Degree of Aggressiveness in Patients with Thyroid Cancer Positive for TERT Promoter Mutations.

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.

The Impact of BRAF V600E Mutation Allele Frequency on the Histopathological Characteristics of Thyroid Cancer.

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.

Coexisting Molecular Alterations Increase the Risk of Malignancy in Thyroid Nodules with Copy Number Alterations.

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.

Molecular Testing for Thyroid Nodules: The Experience at McGill University Teaching Hospitals in 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.

Surgical Outcomes of Thyroid Nodules Positive for Gene Expression Alterations Using ThyroSeq V3 Genomic Classifier.

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.

Thyroglossal duct surgery. What is the acceptable recurrence rate?

OBJECTIVES: To present experiences of different specialties in the treatment of thyroglossal duct cysts (TGDCs) and subsequent complications in multiple centers.  Methods: A retrospective cross-sectional study of all cases of TGDC for a period of 11 years from 2008-2019 by different departments from 3 different centers in Jeddah, Kingdom of Saudi Arabia (King Faisal Specialist Hospital and Research Centre, Bakhsh Hospital and International Medical Center). Results: Forty-nine patients were included. The type of surgery performed plays a significant role in recurrence (p less than 0.001). The Sistrunk procedure had a lower recurrence rate (0%) than simple excision (70%) and has showed a significantly long recurrence-free interval (p less than 0.001). Higher recurrence rates are associated with higher postoperative complications (p=0.002). Patients who underwent pre-operative fine needle aspiration did not have any recurrence during the follow-up period. Conclusion: The Sistrunk procedure is the gold standard technique with the highest recurrence-free interval rate. Fine needle aspiration could be recommended as a less invasive procedure to exclude malignancy.

Rare presentation of metastatic renal cell carcinoma to thyroid gland: A case report.

INTRODUCTION: Renal cell carcinoma is known to cause metastasis to unusual sites, but metastasis to the thyroid gland is a rare occurrence, not only that, but 20 years after complete recovery is almost nonexistent. CASE PRESENTATION: We are presenting here a case of 79-year-old female who presented to us for asymptomatic progressive thyroid nodule. She had history of right nephrectomy for renal cell carcinoma 20 years ago. Ultrasound guided fine needle aspiration biopsy (FNAB) of the thyroid was non-diagnostic. Total thyroidectomy of the patient was performed, and histopathological evaluation of the specimen revealed the swelling to be of metastatic in nature secondary to renal cell carcinoma. DISCUSSION: Despite thyroid metastasis being rare, FNAB can prove to be useful tool for diagnosis of thyroid tumors and metastases and can be inconclusive in some cases. Therefore, immunohistochemistry can prove beneficial in diagnosis such cases. CONCLUSION: The diagnosis of renal cell carcinoma metastasis is made after immunohistochemical evaluation of the thyroidectomy specimen with thyroidectomy proving to be the modality of treatment for such cases with no further radiation therapy and a yearly follow up plan to screen for other lesions.

Diagnostic Challenges in Chondroblastic Maxillary Osteosarcoma: A Case Report.

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.

Nerve Block for Septorhinoplasty: A Retrospective Observational Study of Postoperative Complications in 24 Hours.

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.

A Rare Case of Thyroid Metastasis Secondary to Hidden Undiagnosed Lung Adenocarcinoma.

The majority of thyroid lesions are primary in origin while secondary metastases to thyroid are considered a rare incidence. However, presentation of such cases with no signs of lung cancer can be extremely challenging to diagnose. Here, we present a 64-year-old man, an ex-smoker of 70 pack-years, who presented with a complaint of hoarseness of voice with associated dyspnea, choking episodes, weight loss, and hemoptysis. With no investigation abnormalities indicating lung adenocarcinoma, he was transferred to the Otolaryngology Department as being suspicious of thyroid cancer. A laryngoscopy demonstrated an immobile right vocal cord and pooling of secretions while a computed tomography (CT) scan showed a right thyroid lobe nodule, upper mediastinal lymphadenopathy, and pleural effusion. The patient underwent a total thyroidectomy. Biopsies from the lymph nodes and lung were obtained, and all demonstrated lung adenocarcinoma. Thus, a diagnosis of primary lung adenocarcinoma with thyroid and mediastinal lymph nodes metastases was established. Despite being a rare clinical presentation, thyroid metastasis should be considered and evaluated for a primary origin according to the associated clinical history and presentation.

Hoarseness of Voice as a Rare Presentation of Tuberculosis: A Case Report Study.

BACKGROUND: Having hoarseness of voice as the first clinical manifestation of tuberculosis is rare. This atypical presentation causes some confusion since other more common conditions, such as laryngeal carcinoma, present similarly and might require more invasive tests to confirm the diagnosis. CASE PRESENTATION: A 38-year-old male presented to the otorhinolaryngology clinic with a four-month history of change in voice. Laryngoscopy demonstrated a right glottic mass, raising suspicion of laryngeal cancer. The computed tomography showed a mass and incidental finding of opacities in lung apices. Chest x-ray demonstrated findings suggestive of tuberculosis. Polymerase chain reaction and culture of sputum samples confirmed the diagnosis and the patient was started on anti-tuberculosis treatment. CONCLUSION: Despite accounting for only 1% of pulmonary tuberculosis cases and having a similar presentation to laryngeal carcinoma, we recommend considering laryngeal tuberculosis when evaluating hoarseness of voice in endemic areas.