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Purpose of Review: The aim of this study was to provide a timely and relevant review of the latest findings and explore appropriate management of aggressive variants of papillary thyroid cancer (AVPTC)., Recent Findings: In general, AVPTCs tend to exhibit more invasive characteristics, a lack of responsiveness to radioiodine, increased occurrences of regional spreading, distant metastases and higher mortality rates. Meanwhile, each variant showcases unique clinical and molecular profiles., Summary: Given the elevated risk of recurrence postsurgery, a more aggressive strategy may be necessary when suspected preoperatively, particularly for those presenting with invasive features. Decision on the extent of surgical treatment and adjuvant therapy is individualized and made by experienced clinicians and multidisciplinary teams based on the clinical presentation, presence of aggressive features and molecular profile. Future studies on development of personalized medicine and molecular target therapy may offer tailored treatment options., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Multifocality is a frequent feature of papillary thyroid carcinoma (PTC). Its prognostic value is controversial although national guidelines recommend treatment intensification if present. However, multifocality is not a binary but discrete variable. This study aimed to examine the association between increasing number of foci and risk of recurrence following treatment., Methods: 577 patients with PTC were identified with median follow-up of 61 months. Number of foci were taken from pathology reports. Log-rank test was used to assess significance. Multivariate analysis was performed and Hazard Ratios were calculated., Results: Of 577 patients, 206(35%) had multifocal disease and 36(6%) recurred. 133(23%), 89(15%) and 61(11%) had 3+, 4+ or 5+ foci respectively. The 5-year RFS stratified by number of foci was 95%v93% for 2+foci (p = 0.616), 95%v96% for 3+foci (p = 0.198) and 89%v96% for 4+foci (p = 0.022). The presence of 4 foci was associated with an over 2-fold risk of recurrence (HR 2.296, 95% CI 1.106-4.765, p = 0.026) although this was not independent of TNM staging. Of the 206 multifocal patients, 31(5%) had 4+foci as their sole risk factor for treatment intensification., Conclusion: Although multifocality per se does not confer worse outcome in PTC, finding 4+foci is associated with worse outcome and could therefore be appropriate as a cut-off for treatment intensification. In our cohort, 5% of patients had 4+foci as a sole indication for treatment intensification, suggesting that such a cut off could impact clinical management., Competing Interests: Declaration of competing interest None noted., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: To review the clinical presentation, diagnosis, pathology and management strategies in a modern cohort of patients with thyroglossal duct cyst carcinoma., Study Design: Retrospective case series following PROCESS Guidelines., Setting: Comprehensive cancer centre., Methods: Data recorded included: gender, age at diagnosis, clinical presentation, thyroid function, diagnostic investigations, cytological results, final histology, staging and follow up status. The risk of malignancy in cytological analysis was stratified according to the Royal College of Pathologists classification in United Kingdom., Results: Twelve patients were included. The majority of patients (66.7%) presented with an isolated thyroglossal duct cyst. Only 4 patients had preoperative cytological suspicion of carcinoma (sensitivity: 33.3%). At the time of presentation all patients were euthyroid. Following diagnosis of malignancy, a total thyroidectomy was performed in all patients, with the exception of 2, who had a thyroglossal duct cyst carcinoma of less than 10mm. Among the 10 patients who underwent total thyroidectomy, 7 (70%) patients had proven carcinoma in the thyroid gland, 3 with deposits of less than 10mm. The average size of the thyroid cancer deposits was 7.2mm (1-20mm). With a mean follow-up of is 44 months (5-120), all patients were alive and free of recurrence at the end of the study period., Conclusion: Thyroglossal duct cyst carcinoma is a rare condition and its management should be discussed in a multidisciplinary meeting. As with differentiated thyroid cancer originating in the thyroid gland, it bears extraordinary survival rates. Accordingly, the management of these cancers has shifted towards a more conservative approach although its peculiarities must be taken into account: ease of extracystic invasion and possible different lymph node invasion., (Copyright © 2022 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose of Review: To highlight recent advances in our understanding of the epidemiology, incidence, evaluation, management and outcomes of primary thyroid lymphoma (PTL), and highlight the indications and limitations of surgery., Recent Findings: The differential diagnosis of a rapidly enlarging thyroid mass with or without obstructive symptoms should include PTL and anaplastic thyroid cancer. When PTL is suspected, initial investigations should include blood tests and ultrasound-guided biopsy preferably core need biopsy to allow tissue typing and immunohistochemistry analysis. Systemic imaging with FDG PET-CT is required for staging. Surgery is not recommended for treatment purposes and should be reserved for diagnosis and airway management. Treatment includes chemotherapy and radiotherapy and offer an excellent prognosis., Summary: PTL is a rare malignancy making diagnosis and management challenging. Initial investigations of suspected PTL should include blood tests and ultrasound-guided biopsy, preferably core needle biopsy and systemic imaging is required for staging. Surgery is reserved for diagnosis and airway management. Chemotherapy and radiotherapy are the treatment of choice., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Graves' disease (GD) can be managed by antithyroid drugs (ATD), radioactive iodine (RAI) and surgery. Thyroidectomy offers the highest success rates for both primary and persistent disease, yet it is the least recommended or utilized option reaching <1% for primary disease and <25% for persistent disease. Several surveys have found surgery to be the least recommended by endocrinologists worldwide. With the development of remote access thyroidectomies and intraoperative nerve monitoring of the recurrent laryngeal nerve, combined with current knowledge of possible risks associated with RAI or failure of ATDs, revaluation of the benefit to harm ratio of surgery in the treatment of GD is warranted. The aim of this review is to discuss possible reasons for the low proportion of surgery in the treatment of GD, emphasizing an evidence-based approach to the clinicians' preferences for surgical referrals, surgical indications and confronting traditional reasons and concerns relating to the low referral rate with up-to-date data., (© 2021 John Wiley & Sons Ltd.)

Most cases of thyroid carcinoma are classified as low risk. These lesions have been treated with open surgery, remote access thyroidectomy, active surveillance, and percutaneous ablation. However, there is lack of consensus and clear indications for a specific treatment selection. The objective of this study is to review the literature regarding the indications for management selection for low-risk carcinomas. Systematic review exploring inclusion and exclusion criteria used to select patients with low-risk carcinomas for treatment approaches. The search found 69 studies. The inclusion criteria most reported were nodule diameter and histopathological confirmation of the tumor type. The most common exclusions were lymph node metastasis and extra-thyroidal extension. There was significant heterogeneity among inclusion and exclusion criteria according to the analyzed therapeutic approach. Alternative therapeutic approaches in low-risk carcinomas can be cautiously considered. Open thyroidectomy remains the standard treatment against which all other approaches must be compared., (© 2021 Wiley Periodicals LLC.)

Introduction: Multifocality is increasingly observed in papillary thyroid carcinoma (PTC) due to improvements in imaging and histopathological analysis. However, its significance in management, particularly as a sole risk-factor, remains controversial. This study aimed to investigate the prognostic value of multifocality in predicting recurrence following thyroid lobectomy in a contemporary group of PTC patients managed in the UK., Methods: Patients with PTC in NHS Lothian (2009-19) and Guys and St Thomas NHS Foundation Trust (2012-19) were identified. Categorical variables were compared using Chi-squared or Fisher's exact test. Five-year recurrence free survival (RFS) were analysed using Kaplan-Meier method and compared using log-rank., Results: Of 828 patients; 492 (59%) had unifocal and 336 (41%) multifocal disease on final pathology. A higher rate of pathological nodal disease (22%v36%,p < 0.001), total thyroidectomy (TT) (78%v92%,p < 0.001) and radioactive iodine (RAI) (57%v75%,p < 0.001) was demonstrated in patients with multifocality. With a median follow-up of 50 months, overall 5-year RFS was 96.5%; 96.5% for unifocal versus 96.6% for multifocal disease (p = 0.695). Recurrence was not shown to be associated with multifocality on either univariate or multivariate analysis. Amongst patients with T1/2N0M0 disease (n = 341), more patients were treated with TT and RAI with multifocal compared to unifocal disease (<0.001). Only two patients within this group recurred during follow up, both of whom had multifocal disease and were treated with TT and RAI (5yRFS100%v98.1%,p = 0.051)., Conclusion: Multifocality is a common feature of PTC but does not appear to be an independent predictor of outcome. Therefore, treatment intensification on the basis of multifocality alone seems unwarranted., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Purpose: In the case of well-differentiated thyroid cancer, the importance of microscopic margin status remains controversial. We discuss the relevance of the effect of microscopic positive surgical margins in the early stages of differentiated thyroid cancer., Methods: A comprehensive literature search and review of available evidence in English literature was undertaken., Results: A previous meta-analysis did not find an association between microscopic positive surgical margins and local recurrence. Heterogeneity of definitions and differences between microscopic surgical margins and extrathyroid extension are discussed. Impact on clinical decision-making is explored., Conclusion: The finding of microscopic positive surgical margins in a patient with a thyroid tumor without intraoperative evidence of macroscopic invasion to adjacent structures, with complete resection made by the surgeon and without pathological report of extrathyroid extension, does not have a worse prognostic effect. We present a classification of surgical margins that may help thyroid oncology teams to tailor further management in patients with thyroid cancer.

Introduction: Aggressive variants of papillary thyroid cancer (PTC) have been described with increasing frequency. These variants include diffuse sclerosing variant, tall cell variant, columnar cell variant, solid variant, and hobnail variant., Methods: We have performed a review of the more aggressive variants of PTC with respect to main characteristics, histological and molecular features, and the consequences that the knowledge of these variants should have in the treatment of the patients., Results: At the present time, we do not know the prognostic value of these aggressive PTC variants. The extent of the surgical treatment and adjuvant therapy necessary should be decided on the basis of the extent of the tumor at presentation and the opinion of experienced clinicians., Conclusion: These aggressive variants should be known by clinicians, to avoid underdiagnosis, and treated according to the latest recommendations in the literature.

With improved understanding of the biology of differentiated thyroid carcinoma its management is evolving. The approach to surgery for the primary tumour and elective nodal surgery is moving from a "one-size-fits-all" recommendation to a more personalised approach based on risk group stratification. With this selective approach to initial surgery, the indications for adjuvant radioactive iodine (RAI) therapy are also changing. This selective approach to adjuvant therapy requires understanding by the entire treatment team of the rationale for RAI, the potential for benefit, the limitations of the evidence, and the potential for side-effects. This review considers the evidence base for the benefits of using RAI in the primary and recurrent setting as well as the side-effects and risks from RAI treatment. By considering the pros and cons of adjuvant therapy we present an oncologic surgical perspective on selection of treatment for patients, both following pre-operative diagnostic biopsy and in the setting of a post-operative diagnosis of malignancy., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declar., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose of Review: To highlight recent advances in our understanding of the nature of micropapillary thyroid carcinoma (mPTC), its evaluation and options of management based on risk., Recent Findings: A dramatic increase of the incidence of papillary thyroid carcinoma has been reported worldwide during recent decades, specifically those smaller than 10 mm (mPTC). Although not taking into consideration other risk factors for aggressiveness when describing tumours by their size, most of these newly diagnosed mPTC are indolent and active surveillance can be considered as valid option for their management., Summary: An increasing number of patients with mPTC will be encountered in clinical practice. Although it is difficult to assess the aggressiveness of a tumour on size criteria, less than a total thyroidectomy and active surveillance can be considered for the majority of patients with mPTC. Further trials should be performed to prove this as a valid option of management in the majority of these patients.

The central compartment is a common site for nodal spread from differentiated thyroid carcinoma, often occurring in patients without clinical or ultrasonographic (US) evidence of neck lymph node metastasis (cN0). However, the role of elective central compartment neck dissection (CND) among patients with DTC remains controversial. We performed a systematic literature review, also including review of international guidelines, with discussion of anatomic and technical aspects, as well as risks and benefits of performing elective CND. The recent literature does not uniformly support or refute elective CND in patients with DTC, and therefore an individualized approach is warranted which considers individual surgeon experience, including individual recurrence and complication rates. Patients (especially older males) with large tumors (>4 cm) and extrathyroidal extension are more likely to benefit from elective CND, but elective CND also increases risk for hypoparathyroidism and recurrent nerve injury, especially when operated by low-volume surgeons. Individual surgeons who perform elective CND must ensure the number of central compartment dissections needed to prevent one recurrence (number needed to treat) is not disproportionate to their individual number of central compartment dissections per related complication (number needed to harm)., (Published by Elsevier Ltd.)

Introduction: Around 10% of patients with non-medullary thyroid cancer (NMTC) will have a positive family history for the disease. Although many will be sporadic, families where 3 first-degree relatives are affected can be considered to represent true familial non-medullary thyroid cancer (FNMTC). The genetic basis, impact on clinical and pathological features, and overall effect on prognosis are poorly understood., Methods: A literature review identified articles which report on genetic, clinical, therapeutic and screening aspects of FNMTC. The results are presented to allow an understanding of the genetic basis and the impact on clinical-pathological features and prognosis in order to inform clinical decision making., Results: The genetic basis of FNMTC is unknown. Despite this, significant progress has been made in identifying potential susceptibility genes. The lack of a test for FNMTC has led to a clinical definition requiring a minimum of 3 first-degree relatives to be diagnosed with NMTC. Although some have shown an association with multi-centric disease, younger age and increased rates of extra-thyroidal extension and nodal metastases, these findings are not supported by all. The impact of FNMTC is unclear with all groups reporting good outcome, and some finding an association with more aggressive disease. The role of screening remains controversial., Conclusion: FNMTC is rare but can be diagnosed clinically. Its impact on prognostic factors and the subsequent role in influencing management is debated. For those patients who present with otherwise low-risk differentiated thyroid cancer, FNMTC should be included in risk assessment when discussing therapeutic options., Competing Interests: No authors have a conflict of interest to disclose., (Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Invasive disease is a poor prognostic factor for patients with differentiated thyroid cancer (DTC). Uncontrolled central neck disease is a common cause of distressing death for patients presenting in this manner. Advances in assessment and management of such cases have led to significant improvements in outcome for this patient group. This article reviews the patterns of invasion and a contemporary approach to investigation and treatment of patients with invasive DTC., Summary: Aerodigestive tract invasion is reported in around 10% of case series of DTC. Assessment should include not only clinical history and physical examination with endoscopy as indicated, but ultrasound and contrast-enhanced cross-sectional imaging. Further studies including positron emission tomography should be considered, particularly in recurrent cases that are radioactive iodine (RAI) resistant. Both the patient and the extent of disease should be carefully assessed prior to embarking on surgery. The aim of surgery is to resect all gross disease. When minimal visceral invasion is encountered early, "shave" procedures are recommended. In the setting of transmural invasion of the airway or esophagus, however, full thickness excision is required. For intermediate cases in which invasion of the viscera has penetrated the superficial layers but is not evident in the submucosa, opinion is divided. Early reports recommended an aggressive approach. More recently authors have tended to recommend less aggressive resections with postoperative adjuvant therapies. The role of external beam radiotherapy continues to evolve in DTC with support for its use in patients considered to have RAI-resistant tumors., Conclusions: Patients with invasive DTC require a multidisciplinary approach to investigation and treatment. With detailed assessment, appropriate surgery, and adjuvant therapy when indicated, this patient group can expect durable control of central neck disease, despite the aggressive nature of their primary tumors., Competing Interests: Author Disclosure Statement Dr. Kate Newbold has consultancy and advisory roles with Eisai, Astra-Zeneca, and Genzyme. The other authors have nothing to disclose.

Differentiated thyroid cancer (DTC) accounts for over 90 % of thyroid malignancies, and is frequently associated with central neck compartment nodal metastasis that requires a therapeutic central compartment neck dissection (CCND) for clinically evident nodes. Current knowledge on the expected lymph node yield from a CCND is limited, compared with data on the lateral neck. The aim of our study was to accurately quantify nodal yield from the cadaveric central neck compartment. Twenty-eight cadaveric necks were dissected and the central neck compartment was subdivided into four regions: pre-laryngeal (delphian), pre-tracheal, right and left para-tracheal regions. Each cadaver had a thyroid gland, which was also removed, and the CCND tissue in each compartment was processed and examined by a consultant histopathologist. Only lymphoid tissue with a defined microscopic fibrous capsule and subcapsular sinus was included in the node count. The median total lymph node count per cadaver was four (range 1-16), with a median of one node detectable in each para-tracheal region (range 0-7) and the pre-tracheal region (range 0-8). The median pre-laryngeal node count was 0 (range 0- 2). The average lymph node size across all compartments was 2.9 mm. This is the first European study to assess cadaveric central neck lymph nodes and establish baseline counts for nodal yield. If a prophylactic or therapeutic CCND is required during thyroid surgery, those involved in DTC management must recognise that there is a wide range, and low median yield of central neck compartment lymph nodes.

Purpose of Review: To highlight recent advances in our understanding of the incidence of multinodular goitre (MNG) risk of malignancy, evaluation of patients with MNG, rates and factors predictive of malignancy in MNG, and the choice of surgical procedure for patients with neoplastic MNG., Recent Findings: The incidence of MNG when screened by ultrasound scanning (USS) is between 10 and 20% and when using high resolution USS can be up to 70%. The incidence of occult malignancy within MNG lies between 10 and 35% in surgical series. Younger patients and men have higher rates of malignancy, as do patients with a family history, prior irradiation and those with signs of compressive or invasive disease. Subtotal thyroidectomy has been rejected in favour of either total lobectomy or total thyroidectomy for most patients with MNG., Summary: An increasing number of patients with MNG will be encountered in surgical practice. Most patients can be cured with total lobectomy or total thyroidectomy, which minimizes recurrence rates and ensures an oncological approach to patients with incidentally discovered malignancy within MNG.

Background: The current management of thyroid lymphomas (TL) includes the combined use of chemotherapy and radiotherapy, with surgery mainly confined to diagnosis through an open biopsy following ultrasound-guided fine-needle aspiration cytology (US-FNAC)., Aims: To analyse the clinical presentation and methods of diagnosis of TL, its pitfalls and the management of these tumours presenting with compression symptoms and airway obstruction., Methods: A retrospective review of nine patients diagnosed with TL at Guy's and St Thomas Hospital NHS Foundation Trust in London over the past 5 years., Results: Nine consecutive patients were identified with the diagnosis of TL, and seven (78%) of them being women and with a mean age of 65 years. All patients presented with an anterior neck mass while four (44.4%) presented with stridor and vocal cord palsy. Two (22.2%) presented with a hoarse voice, dysphagia, and only one patient had a B symptom of weight loss. FNAC was diagnostic in three patients (33.3%) and a report of multi-nodular goitre in one patient. There was clinical suspicion of TL in three patients (33.3%). Of the three patients presenting with stridor, two had an open biopsy followed by the initiation of dexamethasone therapy and resolution of symptoms within 48 h. One patient had a partial thyroidectomy following a suspected diagnosis of multi-nodular goitre from US-FNAC. One patient required tracheostomy for airway management., Conclusion: Diagnosis of TL may be difficult. However, US-FNAC is useful in raising the suspicion of a TL. Open biopsy is still the definitive diagnostic tool of choice. In the emergency setting of airway obstruction, once definitive diagnosis is achieved, dexamethasone therapy and endotracheal intubation for airway management are all that is required for optimal management strategy. Surgical intervention has no role except for providing tissue for diagnosis.

Background: Recurrent laryngeal nerve palsy (RLNP) is a recognised possible complication after thyroid surgery. It may present with a variety of symptoms, such as voice change and respiratory symptoms. However, it may remain undetected and the true incidence may be under-reported. The aim of this study was to determine the reported incidence of temporary and permanent palsy after thyroid surgery using different vocal assessment methods., Methods: A Medline search was performed. A systematic review was undertaken which included 27 articles and 25,000 patients., Results: The average incidence of temporary RLNP after thyroid operations is 9.8% and the incidence of permanent RLNP is 2.3%. The RLNP rate varied according to the method of examining the larynx and ranged from 26% to 2.3%. Most of the reviewed studies recommend a follow-up period up to 1 year to assess and evaluate RLNP., Conclusion: Our study has identified that different methods are used to diagnose RNLP and that a wide variety of reported RLNP rates exist. We propose establishment of a 'gold standard' for assessing the voice after thyroidectomy to reduce reporting bias.

Thyroid lobectomy with isthmusectomy is the standard surgical technique for removal of unilateral thyroid nodules, and it involves the exposure of the tracheoesophageal grooves. Thyroid isthmusectomy is a surgical procedure that excises only the thyroid isthmus. It allows excision of a lesion without the exposure of the tracheoesophageal grooves. We aimed to demonstrate that isthmusectomy could be a safe alternative to thyroid lobectomy with isthmusectomy in patients with nodules confined to the isthmus or the pyramidal lobe. This was a prospective study performed over a five year period from 1999 to 2004. Inclusion criteria for thyroid isthmusectomy were: patients with a single lesion located in the region of the thyroid isthmus or the pyramidal lobe; maximum lesion diameter of 30 mm; and cytological reports of non-diagnostic appearance, follicular cells or suspicion of malignancy. Nine patients were identified with these criteria. Histology included two colloid nodules, three benign follicular adenomas, two Hurthle cell adenomas and two papillary thyroid carcinomas. There were no recorded complications. Thyroid isthmusectomy is a safe alternative to thyroid lobectomy with isthmusectomy in patients who have nodules confined to the isthmus and pyramidal lobe. Leaving a cuff of normal thyroid tissue has the advantage of not exposing the tracheoesophageal grooves, thus minimising potential damage to the recurrent laryngeal nerves and parathyroids. Surgeons performing isthmusectomies should be experienced in more complex thyroid surgical procedures.