CD4+ T cell activation distinguishes response to anti-PD-L1+anti-CTLA4 therapy from anti-PD-L1 monotherapy.

Cancer patients often receive a combination of antibodies targeting programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen-4 (CTLA4). We conducted a window-of-opportunity study in head and neck squamous cell carcinoma (HNSCC) to examine the contribution of anti-CTLA4 to anti-PD-L1 therapy. Single-cell profiling of on- versus pre-treatment biopsies identified T cell expansion as an early response marker. In tumors, anti-PD-L1 triggered the expansion of mostly CD8+ T cells, whereas combination therapy expanded both CD4+ and CD8+ T cells. Such CD4+ T cells exhibited an activated T helper 1 (Th1) phenotype. CD4+ and CD8+ T cells co-localized with and were surrounded by dendritic cells expressing T cell homing factors or antibody-producing plasma cells. T cell receptor tracing suggests that anti-CTLA4, but not anti-PD-L1, triggers the trafficking of CD4+ naive/central-memory T cells from tumor-draining lymph nodes (tdLNs), via blood, to the tumor wherein T cells acquire a Th1 phenotype. Thus, CD4+ T cell activation and recruitment from tdLNs are hallmarks of early response to anti-PD-L1 plus anti-CTLA4 in HNSCC.

Initial surgical management of sporadic medullary thyroid cancer: Guidelines based optimal care - A systematic review.

INTRODUCTION: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor from parafollicular cells that produce calcitonin (Ct). Despite several existing guidelines for the surgical management of sporadic MTC (sMTC), optimal initial surgical management of the thyroid, the central and the lateral neck remains a matter of debate. METHODS: A systematic review in PubMed and Scopus for current guidelines addressing the surgical management of sMTC and its referenced citations was conducted as per the PRISMA guidelines. RESULTS: Two-hundred and one articles were identified, of which 7 met the inclusion criteria. Overall, guidelines vary significantly in their recommendations for the surgical management of sMTC. Only one guideline recommended partial thyroidectomy for limited disease, but the possibility to avoid completion thyroidectomy in selected cases is acknowledged in 42% (3/7) of the remaining guidelines. The majority of guidelines (71.4%; 5/7) recommended prophylactic central neck dissection (CND) for all patients while the remaining two guidelines recommended CND based on Ct level and tumor size. The role of prophylactic lateral neck dissection based on preoperative Ct levels was recommended by 42% (3/7) of guidelines. Overall, these guidelines are based on low-quality evidence, mostly single-center retrospective series, some of which are over 20 years old. CONCLUSION: Current surgical management guidelines of sMTC should be revised, and ought to be based on updated data challenging current recommendations, which are based on historic, low-quality evidence. Partial thyroidectomy may become a viable option for small, limited tumors. Prospective, multi-center studies may be useful to conclude whether prophylactic ND is necessary in all sMTC patients.

The prognostic effect of radiological extranodal extension in HPV-positive oropharyngeal squamous cell carcinomas: a retrospective cohort analysis.

PURPOSE: Radiological extranodal extension (rENE) is a well-known negative prognosticator in head and neck squamous cell carcinoma (HNSCC). However, controversy remains regarding the prognostic effect of rENE in HPV-positive oropharyngeal SCCs (OPSCC). This single-center retrospective cohort analysis assessed the prognostic role of rENE in an HPV + OPSCC population and tried to validate a recently proposed modification of the TNM8 N-classification. METHODS: 129 patients with HPV + OPSCC, of whom 106 cN + patients, were included. Radiological imaging (CT, MRI or both) was reanalyzed by a senior head and neck radiologist. Overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRFS), and disease-specific survival (DSS) were evaluated. Cox proportional hazard models were used for estimating hazard ratios (HR). RESULTS: A non-significant trend towards better outcomes in the rENE- group, as compared to the rENE + population, was observed for 5 year OS [80.99% vs 68.70%, HR: 2.05, p = 0.160], 5 year RFS [78.81% vs 67.87%, HR: 1.91, p = 0.165], 5 year DFS [77.06% vs 60.16%, HR: 2.12, p = 0.0824] and 5 year DSS [88.83% vs 81.93%, HR: 2.09, p = 0.195]. OS declined with ascending levels of rENE (p = 0.020). Multivariate analysis identified cT-classification and smoking as independent negative predictors for OS/DFS. The proposed modification of the TNM8 N-classification could not be validated. CONCLUSIONS: Although rENE could not be identified as an independent negative prognosticator for outcome in our HPV + OPSCC population, outcomes tend to deteriorate with increasing rENE.

Complications related to the Cook-Swartz implantable Doppler probe use in head and neck microvascular reconstruction: a systematic review.

PURPOSE: Vascular perfusion research has been dedicated to identify inexpensive, effective, and easy to use methods to assess free flap perfusion for both buried and non-buried flaps. METHODS: Systematic review of complications in patients underwent Head and Neck microsurgical reconstruction and vascular implantable Doppler monitoring. RESULTS: Sixteen articles were included for qualitative analysis. 2535 (92.2%) patients received IDP monitorization. Venous thrombosis was the most common vascular complication effecting 28 (1.1%). Regarding complications potentially related to the use of the IDP, just one study described the presence of granuloma formation along the suture line in 2 (0.07%) patients. CONCLUSIONS: Our findings indicated that Cook-Swartz IDP will represents a safe and effective device for FF monitoring in HN reconstructive micro-surgery. A detailed prospective registration of the results and complications related to the use of IDP remains mandatory to precisely estimate results, cost, and complications.

Customized Nasal Prosthesis for a Jones Lacrimal Bypass Tube Using 3-Dimensional Planning and Printing Technology.

A 35-year-old woman was treated for extensive squamous cell carcinoma of the nasal septal mucosa with total rhinectomy, including removal of the nasal septum, and chemoradiotherapy. A magnet-retained nasal prosthesis was fitted. She had developed right-sided epiphora from total proximal lacrimal canalicular obstruction, for which an angled Jones lacrimal bypass tube was inserted. The tube, however, intermittently rotated in the nasal cavity, causing recurrent epiphora and irritation at the caruncular site. With the aid of 3-dimensional technology, we designed a septum for the prosthesis that stabilized the tube within the nasal cavity. At the follow-up 2 years later, the patient was satisfied with the nasal prosthesis and lacrimal stent. To our knowledge, this report is the first to describe a patient-specific nasal prosthesis adapted for a Jones tube after total rhinectomy.

Clear Cell Neoplasms of Salivary Glands: A Diagnostic Challenge.

This review focuses on the heterogenous group of clear cell neoplasms of salivary glands and attempts to identify major differential diagnostic features. Within the head and neck region, clear cells are found most commonly in salivary gland tumors, but may also be seen in tumors of squamous or odontogenic epithelial origin, primary or metastatic carcinomas, benign or malignant melanocytic lesions, or benign or malignant mesenchymal tumors. Clear cells occur fairly commonly among a wide variety of salivary gland neoplasms, but mostly they constitute only a minor component of the tumor cell population. Clear cells represent a major diagnostic feature in two salivary gland neoplasms, epithelial-myoepithelial carcinoma and hyalinizing clear cell carcinoma. In addition, salivary gland neoplasms composed predominantly of clear cells could also include clear cell variants of other salivary neoplasms, such as mucoepidermoid carcinoma and myoepithelial carcinoma, but their tumor type-specific histologic features may only be available in limited nonclear cell areas of the tumor. Diagnosing predominantly clear cell salivary gland tumors is difficult because the immunoprofiles and morphologic features may overlap and the same tumor entity may also have a wide range of other histologic presentations. Many salivary gland tumors are characterized by tumor type-specific genomic alterations, particularly gene fusions of the ETV6 gene in secretory carcinoma, the MYB and MYBL1 genes in adenoid cystic carcinoma, the MAML2 gene in mucoepidermoid carcinoma, the EWSR1 gene in hyalinizing clear cell carcinoma, and others. Thus, along with conventional histopathologic examination and immunoprofiling, molecular and genetic tests may be important in the diagnosis of salivary gland clear cell tumors by demonstrating genetic alterations specific to them.

Long-term follow-up of the inside-out technique for treatment of preauricular sinuses: observational study.

PURPOSE: This long-term follow-up study aims to externally validate the inside-out technique for surgical treatment of preauricular sinuses. METHODS: We analyzed the medical records of all patients who underwent the IO procedure at University Hospitals Leuven from 1 November 2005 to 30 November 2019 (N = 110). We were able to contact 77 of these 110 patients for a telephone interview, where we used a standardized questionnaire to evaluate recurrence, patient satisfaction and aesthetic result. RESULTS: We studied 110 patients (68 males, 77 females), resulting in 145 PAS (35 left, 40 right, 35 bilateral), with a median follow-up of 53 months. Fifteen PAS (10.3%) developed an early (< 4 weeks) postoperative complication (wound dehiscence, infection, abcedation, swelling). Two PAS (2 different patients) needed revision surgery because of recurrence, one after 15 months, the other after 4 years. The 5-year Kaplan-Meier recurrence-free percentage was 97.7%, equating to an estimated recurrence rate of 2.3%. Ninety-four percent was satisfied with the aesthetic result, giving 4 or 5 points on a 5-point Likert scale. CONCLUSIONS: This study was able to externally validate the IO technique for the treatment of PAS. The IO technique should be first choice, since it guarantees low recurrence rates, excellent aesthetic results, and good patient satisfaction.

Long-term outcome of a cohort of 272 patients undergoing sialendoscopy.

OBJECTIVES: To assess the cohort of patients undergoing sialendoscopic intervention for improvement of symptoms and gland-related quality of life at long-term follow-up. DESIGN: This is a retrospective review of medical records with a prospective follow-up by questionnaire. SETTING & PARTICIPANTS: All patients undergoing sialendoscopy at the University Hospitals Leuven Department of Otorhinolaryngology, Head and Neck Surgery between March 2008 and June 2020. MAIN OUTCOME MEASURES: The electronic files of the patients were searched for information about their sialendoscopic procedure and follow-up consultations. We also send the patients a questionnaire by mail to assess symptom control and gland-related quality of life at long-term follow-up. RESULTS: Two hundred seventy-two sialendoscopies were performed in 221 patients. Median follow-up time was 37 months. The sialendoscopies were performed in 130 patients for lithiasis, in 66 for stenosis, in 14 for recurrent parotitis of childhood, in 8 for recurrent sialadenitis of unknown origin and in 3 for radioiodine-induced sialadenitis. Complications occurred in 11 of 272 sialendoscopies (4%). Those were iatrogenic perforations, temporary lingual nerve paresthesia and swelling of the floor of the mouth. 53% of patients returned the questionnaire, for a total of 146 evaluable sialendoscopies. The majority of the responders indicated that sialendoscopy had improved their symptoms (83.6%). Salivary glands could be preserved in 89% of the responder group. The highest percentage of patients reporting residual symptoms was found in the RPC group (81.3%) and the lowest in the lithiasis group (16.2%). Besides age, no statistical differences in demographic and pathological features between the responder and non-responder groups were found, supporting generalisation of the responders' results to the entire cohort. CONCLUSIONS: This study confirms the good long-term outcomes of sialendoscopic interventions in patients with chronic sialadenitis of different aetiologies and a high rate of gland preservation.

Glue embolization of a bleeding lingual artery pseudoaneurysm related to tongue surgery.

Postoperative lingual artery pseudoaneurysm associated with hemorrhage is a rare entity mainly found after tonsillectomy or laryngectomy. In this report, a symptomatic, lingual artery pseudoaneurysm after repeated base of tongue surgery was identified on computed tomography and successfully managed with catheter-directed glue-embolization.

Oncologic Outcomes After Salvage Laryngectomy for Squamous Cell Carcinoma of the Larynx and Hypopharynx: A Multicenter Retrospective Cohort Study.

OBJECTIVE: We aimed to analyze oncologic outcomes and identify patterns of failure and negative prognostic factors in patients who underwent salvage total laryngectomy (STL) for residual, recurrent, and second primary squamous cell carcinoma (SCC) of the larynx and hypopharynx. METHODS: This was a retrospective cohort study of patients who underwent STL in four major Belgian reference hospitals between 2002 and 2018 for residual/recurrent/second primary SCC in the larynx or hypopharynx after initial (chemo)radiation. Prognostic factors for oncologic outcomes were identified using univariable and multivariable analysis. RESULTS: A total of 405 patients were included in the final analysis. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and locoregional relapse-free survival (LRFS) estimates were 47.7% (95% confidence interval [CI] 42.0-53.2%), 68.7% (95% CI 63.7-73.7%), 42.1% (95% CI 36.7-47.4%), and 44.3% (95% CI 38.8-49.7%), respectively. In a multivariable model, increasing clinical tumor stage of the residual/recurrent/second primary tumor, increasing number of metastatic cervical lymph nodes retrieved during neck dissection, hypopharyngeal and supraglottic tumor location, positive section margin status and perineural invasion were independent negative prognostic variables for OS, DSS, DFS, and LRFS. The type of second tumor was identified as an additional independent prognosticator for DSS, with local recurrences and second primary tumors having a better prognosis than residual tumor. CONCLUSIONS AND RELEVANCE: Favorable oncologic outcomes are reported after STL. Increasing clinical tumor stage, increasing number of metastatic cervical lymph nodes, hypopharyngeal and supraglottic tumor location, positive section margins, and perineural invasion are identified as independent negative prognosticators for all oncologic outcome measures.

Pleomorphic adenoma: the great mimicker of malignancy.

Pleomorphic adenoma (PA) is the most common salivary gland neoplasm, and its diagnosis is straightforward in the majority of cases. However, not infrequently, PA shows unusual and uncommon histological features that can be confused with those of malignancy. The difficulties in diagnosing PA arise from its ability to mimic invasion, show atypical or metaplastic cytomorphology, and show morphological features that overlap with those of established salivary gland carcinomas. In addition, recognising early malignant transformation to carcinoma ex-pleomorphic adenoma continues to be a frequent challenge. This review describes the diagnostic pitfalls of PA, and offers a systematic approach to avoid them by combining classic histopathology with novel immunohistochemical and molecular tests.

High-grade Transformation/Dedifferentiation in Salivary Gland Carcinomas: Occurrence Across Subtypes and Clinical Significance.

High-grade transformation (HGT) or dedifferentiation has been described in a variety of salivary gland carcinomas, including acinic cell carcinoma, secretory carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous adenocarcinoma, low-grade mucoepidermoid carcinoma, and hyalinizing clear cell carcinoma. High-grade (HG) transformed tumors are composed of a conventional low-grade component characterized by specific microscopic and immunohistochemical features for the given entity, intermingled with or juxtaposed to areas of HG morphology. This is usually either poorly differentiated adenocarcinoma, carcinoma not otherwise specified, or undifferentiated carcinoma, in which the original line of differentiation is lost. The HG component is composed of solid nests of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli, and abundant cytoplasm. Frequent mitoses and extensive necrosis may be present. The Ki-67 labeling index is consistently higher in the HG component. The molecular genetic mechanisms responsible for HGT of salivary gland carcinomas are largely unknown, though p53 inactivation and human epidermal growth factor receptor 2 overexpression and/or gene amplification have been demonstrated in the HG component in a few examples, the frequency varies for each histologic type. Salivary gland carcinomas with HGT are more aggressive than conventional carcinomas, with a higher local recurrence rate and a poorer prognosis. They have a high propensity for cervical lymph node metastasis suggesting a need for a wider resection and neck dissection. HGT of salivary gland carcinoma can occur either at initial presentation or less commonly at the time of recurrence, sometimes following postoperative radiotherapy. The potential for HGT in almost any type of salivary gland carcinoma warrants a thorough sampling of all salivary gland malignancies to prevent oversight of a HG component.

Assessing the quality of life of head and neck healthcare workers during the COVID-19 pandemic-A self-reported global cross-sectional questionnaire study by the International Federation of Head and Neck Oncologic Societies.

BACKGROUND: Considering the pandemic's mode of transmission, the impact on quality of life (QOL) is likely to be exaggerated among healthcare workers (HCWs) who treat head and neck diseases (hHCWs). METHODS: A cross-sectional self-reported QOL assessment was undertaken between July and September 2020 using the World Health Organization Quality of Life instrument sent out to hHCWs. Factors that predicted a poorer QOL were identified using regression models and mediation analysis. RESULTS: Responses from 979 individuals across 53 countries were analyzed with 62.4% participation from low- and middle-income countries. The physical domain had the highest mean scores of 15 ± 2.51, while the environmental domain was the lowest (14.17 ± 2.42). Participants from low- and middle-income countries had a significantly worse physical (p < 0.001) and environmental (p < 0.001) domains, while a low coronavirus disease 2019-related mortality significantly impacted the environmental domain (p-0.034). CONCLUSION: QOL-related issues among hHCWs are a vexing problem and need intervention at an individual and systems level in all parts of the world.

Review of surgical techniques and guide for decision making in the treatment of benign parotid tumors.

PURPOSE: Surgical treatment of benign parotid tumors has developed in the direction of less invasive procedures in recent years and has raised great debate about the best surgical approach. Aim of this article is to analyse anatomical and other factors that are important in selection of the appropriate surgical technique in treatment of benign parotid tumors. Furthermore, to discuss the risk of complications and recurrent disease according to selected operation. Finally, to define patient selection criteria to facilitate decision making in parotid surgery and become a guide for younger surgeons. METHODS: Literature review and authors' personal opinions based on their surgical experience. RESULTS: All possible surgical techniques for benign parotid surgery with advantages and disadvantages are being described. An algorithm with anatomical and other criteria influencing decision making in benign parotid surgery is presented. CONCLUSION: Surgeons nowadays have many options to choose from for benign parotid surgery. ECD is one of the many surgical techniques available in parotid surgery and can achieve excellent results with proper training and if used for proper indications. PSP is mainly indicated in large tumors of the caudal part of the PG (ESGS level II). SP represents a universal solution in parotid surgery and should be the first technique young surgeons learn. TP has only few but important indications in benign parotid surgery. Surgeons need to carefully consider the patient and his/her preoperative imaging as well as her or his own special expertise to select the most appropriate surgical technique.

Salvage carbon dioxide transoral laser microsurgery for laryngeal cancer after (chemo)radiotherapy: a European Laryngological Society consensus statement.

PURPOSE: To provide expert opinion and consensus on salvage carbon dioxide transoral laser microsurgery (CO2 TOLMS) for recurrent laryngeal squamous cell carcinoma (LSCC) after (chemo)radiotherapy [(C)RT]. METHODS: Expert members of the European Laryngological Society (ELS) Cancer and Dysplasia Committee were selected to create a dedicated panel on salvage CO2 TOLMS for LSCC. A series of statements regarding the critical aspects of decision-making were drafted, circulated, and modified or excluded in accordance with the Delphi process. RESULTS: The expert panel reached full consensus on 19 statements through a total of three sequential evaluation rounds. These statements were focused on different aspects of salvage CO2 TOLMS, with particular attention on preoperative diagnostic work-up, treatment indications, postoperative management, complications, functional outcomes, and follow-up. CONCLUSION: Management of recurrent LSCC after (C)RT is challenging and is based on the need to find a balance between oncologic and functional outcomes. Salvage CO2 TOLMS is a minimally invasive approach that can be applied to selected patients with strict and careful indications. Herein, a series of statements based on an ELS expert consensus aimed at guiding the main aspects of CO2 TOLMS for LSCC in the salvage setting is presented.

The Value of Virtual Chromoendoscopy in the Workup of Patients with Head and Neck Squamous Cell Carcinoma.

PURPOSE OF REVIEW: Second primary tumors (SPTs) significantly increase the mortality in patients with head and neck squamous cell carcinomas (HNSCCs). Virtual chromoendoscopy (VCE) could complement or replace lugol chromoendoscopy (LCE) for early esophageal second primary tumor (ESPT) detection. An overview of the existing techniques and their diagnostic performance in early detection of esophageal squamous cell neoplasms is provided. RECENT FINDINGS: Nowadays, LCE is the golden standard to detect ESPTs. Recently, multiple new VCE techniques have been developed. Especially narrow-band imaging (NBI) is promising. It shows similar sensitivity to LCE, but a significantly higher specificity. Patients with HNSCC are prone to develop ESPTs, both synchronous and metachronous, with a substantial negative impact on survival rates. Therefore, active screening and follow-up is necessary. LCE is an effective screening method, but has some disadvantages. Countering these drawbacks, NBI shows a high potential in early ESPT detection in high-risk patients. Additional multicenter studies are needed to compare diagnostic performance and cost-effectiveness of NBI and other VCE techniques with LCE.

Management of the Neck in Well-Differentiated Thyroid Cancer.

PURPOSE OF REVIEW: In this narrative review, we discuss the indications for elective and therapeutic neck dissections and the postoperative surveillance and treatment options for recurrent nodal disease in patients with well-differentiated thyroid cancer. RECENT FINDINGS: Increased availability of advanced imaging modalities has led to an increased detection rate of previously occult nodal disease in thyroid cancer. Nodal metastases are more common in young patients, large primary tumors, specific genotypes, and certain histological types. While clinically evident nodal disease in the lateral neck compartments has a significant oncological impact, particularly in the older age group, microscopic metastases to the central or the lateral neck in well-differentiated thyroid cancer do not significantly affect outcome. As patients with clinically evident nodal disease are associated with worse outcomes, they should be treated surgically in order to reduce rates of regional recurrence and improve survival. The benefit of elective neck dissection remains unverified as the impact of microscopic disease on outcomes is not significant.

Facial nerve electrodiagnostics for patients with facial palsy: a clinical practice guideline.

PURPOSE: Facial nerve electrodiagnostics is a well-established and important tool for decision making in patients with facial nerve diseases. Nevertheless, many otorhinolaryngologist-head and neck surgeons do not routinely use facial nerve electrodiagnostics. This may be due to a current lack of agreement on methodology, interpretation, validity, and clinical application. Electrophysiological analyses of the facial nerve and the mimic muscles can assist in diagnosis, assess the lesion severity, and aid in decision making. With acute facial palsy, it is a valuable tool for predicting recovery. METHODS: This paper presents a guideline prepared by members of the International Head and Neck Scientific Group and of the Multidisciplinary Salivary Gland Society for use in cases of peripheral facial nerve disorders based on a systematic literature search. RESULTS: Required equipment, practical implementation, and interpretation of the results of facial nerve electrodiagnostics are presented. CONCLUSION: The aim of this guideline is to inform all involved parties (i.e. otorhinolaryngologist-head and neck surgeons and other medical specialists, therapeutic professionals and the affected persons) and to provide practical recommendations for the diagnostic use of facial nerve electrodiagnostics.

Vestibular dysfunction is a manifestation of 22q11.2 deletion syndrome.

The 22q11.2 deletion syndrome (22q11.2DS) is the second most common cause of developmental delay after Down syndrome. Impaired cognitive development is highly prevalent, but also motor abnormalities such as hypotonia and delays in achieving motor milestones are described. Instability is frequently detected in children, adolescents, and adults and is mostly attributed to their limited motor performance. Until now, vestibular function has not been investigated in these patients, despite the growing evidence that they often have inner ear malformations. The aim of this prospective study was to identify the presence and character of vestibular dysfunction in 22q11.2DS. We investigated 23 subjects with proven 22q11.2DS, older than the age of 12. We performed caloric testing and pendular rotation chair tests with videonystagmography, cervical vestibular-evoked myogenic potential (c-VEMP)-testing, and posturography. Additional otoscopy and audiometry were performed on all subjects. We found a unilateral caloric hypofunction in 55% of patients, a certain absent c-VEMP response in 15% of ears, an inconclusive c-VEMP response in 33% of ears, and abnormal posturography in 68% of patients, of whom 42% displayed a typical vestibular pattern. Remarkably, 90% revealed uni- or bilateral weak caloric responses, independent of caloric symmetry. Vestibular dysfunction is frequent in subjects with 22q11.2DS. This knowledge should be taken into account when assessing motor performance in these patients. Additional larger studies are needed to determine whether this dysfunction implicates a therapeutic potential.

Surgical management of intrathoracic goitres.

BACKGROUND: Intrathoracic goitres (ITG) often present with compressive symptoms and require specialised care by experienced surgical teams. Most ITG can be accessed by a transcervical approach (TCA) and only between 1 and 15% will require an extracervical approach (ECA). Many controversies exist regarding the clinical presentation, evaluation, selection of cases for ECA, surgical technique and outcomes. This paper reviews the recent literature on the management, outcomes and evidence-based treatment strategies of ITG. METHODS: We conducted a review of the literature on the evaluation, management and outcomes of surgery for ITGs. RESULTS: The incidence of cancer in the ITGs ranges between 4 and 20%. Multiplanar CT scanning offers the best preoperative evaluation and aids to determine the approach. Most ITG can be accessed by TCA and ECA are only needed in maximum 15% of cases. In experienced hands, the outcome of these surgeries is comparable to thyroid surgery for non-ITG. CONCLUSIONS: Surgery for ITG is challenging. The experienced surgeon however, with few exceptions can address ITG via TCA, with outcomes comparable to those of uncomplicated thyroid surgery.