Update on olfactory neuroblastoma.

Olfactory neuroblastomas are uncommon malignancies that arise from olfactory receptor cells located high in the nasal cavity. Accurate diagnosis plays a crucial role in determining clinical results and guiding treatment decisions. Diagnosis can be a major challenge for pathologists, especially when dealing with tumours with poor differentiation. The discovery of several molecular and immunohistochemical markers would help to overcome classification difficulties. Due to the paucity of large-scale studies, standardisation of diagnosis, treatment and prediction of outcome remains a challenge. Surgical resection by endoscopic techniques with the addition of postoperative irradiation is the treatment of choice. In addition, it is advisable to consider elective neck irradiation to minimise the risk of nodal recurrence. Molecular characterisation will help not only to make more accurate diagnoses but also to identify specific molecular targets that can be used to develop personalised treatment options tailored to each patient. The present review aims to summarise the current state of knowledge on histopathological diagnosis, the molecular biology and management of this disease.

Evaluating new treatments for anaplastic thyroid cancer.

INTRODUCTION: Anaplastic thyroid cancer (ATC) is one of the most lethal diseases known to humans with a median survival of 5 months. The American Thyroid Association (ATA) recently published guidelines for the treatment of this dreadful thyroid malignancy. AREAS COVERED: This review presents the current therapeutic landscape of this challenging disease. We also present the results from trials published over the last five years and summarize currently active clinical trials. EXPERT OPINION: Recent attempts to improve the prognosis of these tumors are moving toward personalized medicine, basing the treatment decision on the specific genetic profile of the individual tumor. The positive results of dabrafenib and trametinib for ATC harboring the BRAF V600E mutation have provided a useful treatment option. For the other genetic profiles, different drugs are available and can be used to individualize the treatment, likely using drug combinations. Combinations of drugs act on different molecular pathways and achieve inhibition at separate areas. With new targeted therapies, average survival has improved considerably and death from local disease progression or airway compromise is less likely with improvement in quality of life. Unfortunately, the results remain poor in terms of survival.

Transpharyngeal Approaches for Management of Oropharyngeal Squamous Cell Carcinoma: Mayo Clinic Institution Experience.

OBJECTIVE: Investigate oncologic and functional outcomes associated with transhyoid and lateral pharyngotomy (transpharyngeal) approaches in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). STUDY DESIGN: Retrospective review. SETTING: Single institution (tertiary care center). METHODS: This is a retrospective case series of patients with OPSCC undergoing transpharyngeal resection from 1990 to 2017 at Mayo Clinic. Oncologic outcomes, postoperative complications, objective swallowing data, and rates of tracheostomy and percutaneous gastrostomy tube dependence were recorded. RESULTS: Of 83 patients meeting inclusion criteria, 56 (68%) were human papillomavirus positive. Overall survival rates at 5 and 10 years following surgery were 85% and 80%, respectively. Cancer-specific survival rates at these same time points were 90% and 88%. Following treatment, 35 of 49 patients (71%) had a Functional Oral Intake Scale score ≥5, indicating total oral intake of multiple consistencies; 79 of 82 (96%) were without tracheostomy or laryngectomy; and 71 of 81 (88%) were on a full oral diet. CONCLUSION: Transpharyngeal approaches provide adequate functional and oncologic outcomes in the majority of patients with OPSCC. These results may have important implications for patients who are not candidates for, or are unwilling to undergo, nonoperative therapy or for those without access to radiation therapy.

Revisiting the role of surgery in the treatment of Graves' disease.

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.

The role of total parotidectomy in high-grade parotid malignancy: A multisurgeon retrospective review.

PURPOSE: Determine rates of intra-parotid and neck nodal metastasis, identify risk factors for recurrence, and report outcomes in patients with primary high-grade parotid malignancy who undergo total parotidectomy and neck dissection. MATERIALS & METHODS: Retrospective review of patients undergoing total parotidectomy and neck dissection for high-grade parotid malignancy between 2005 and 2015. The presence and number of parotid lymph nodes, superficial and deep, as well as cervical lymph nodes involved with metastatic disease were assessed. Risk factors associated with metastatic spread to the parotid deep lobe were identified and recurrence rates reported. RESULTS: 75 patients with median follow-up time of 47 months. 35 patients (46.7%) had parotid lymph node metastasis. Seven patients (9.3%) had deep lobe nodal metastasis without metastasis to the superficial lobe nodes. Nine patients (12%) had positive intra-parotid nodes without positive cervical nodes. Cervical nodal disease was identified in 49.3% patients (37/75). Local, parotid-bed recurrence rate was 5.3% (4/75). Regional lymph node recurrence rate was also 5.3% (4/75). Rate of distant metastasis was 30.6% (23/75). The overall disease free survival rate for all patients at 2 and 5 years were 71% and 60% respectively. CONCLUSION: Parotid lymph node metastasis occurred at a similar rate to cervical lymph node metastasis (46.7% and 49.3%, respectively). Deep lobe parotid nodal metastasis occurred in nearly a quarter of patients and can occur without superficial parotid nodal metastasis. Rate of recurrence in the parotid bed, which may represent local or regional recurrence, was similar to regional cervical lymph node recurrence. Total parotidectomy and neck dissection should be considered high-grade parotid malignancy regardless of clinical nodal status.

Current Trends and Controversies in the Management of Warthin Tumor of the Parotid Gland.

PURPOSE: To review the current options in the management of Warthin tumors (WTs) and to propose a working management protocol. METHODS: A systematic literature search was conducted using PubMed and ScienceDirect database. A total of 141 publications were selected and have been included in this review. Publications were selected based on relevance, scientific evidence, and actuality. RESULTS: The importance of parotid WTs is increasing due to its rising incidence in many countries, becoming the most frequently encountered benign parotid tumor in certain parts of the world. In the past, all WTs were treated with surgery, but because of their slow growth rate, often minimal clinical symptoms, and the advanced age of many patients, active observation has gradually become more widely used. In order to decide on active surveillance, the diagnosis of WT must be reliable, and clinical, imaging, and cytological data should be concordant. There are four clear indications for upfront surgery: uncertain diagnosis; cosmetic problems; clinical complaints, such as pain, ulceration, or recurrent infection; and the patient's wish to have the tumor removed. In the remaining cases, surgery can be elective. Active surveillance is often suggested as the first approach, with surgery being considered if the tumor progresses and/or causes clinical complaints. The extent of surgery is another controversial topic, and the current trend is to minimize the resection using partial parotidectomies and extracapsular dissections when possible. Recently, non-surgical options such as microwave ablation, radiofrequency ablation, and ultrasound-guided ethanol sclerotherapy have been proposed for selected cases. CONCLUSIONS: The management of WT is gradually shifting from superficial or total parotidectomy to more conservative approaches, with more limited resections, and to active surveillance in an increasing number of patients. Additionally, non-surgical treatments are emerging, but their role needs to be defined in future studies.

Hürthle Cell Carcinoma of the Thyroid Gland: Systematic Review and Meta-analysis.

INTRODUCTION: Hürthle cell carcinoma (HCC) comprises about 5% of thyroid carcinoma cases. Partly because of its rarity there is much we still need to know about HCC as compared to other histological cancer subtypes. METHODS: We conducted a systematic literature review following PRISMA guidelines and meta-analysis, from 2000 to 2020, to investigate the main characteristics of HCC and clarify information concerning tumor behavior and treatment. RESULTS: Our review included data from 9638 patients reported in 27 articles over the past 20 years. This tumor occurred more frequently in women (67.5%). The mean age was 57.6 years, and the mean size of the neoplasm at diagnosis was 30 mm. Extrathyroidal extension was common (24%) but lymph node metastasis was not (9%). Total thyroidectomy was the most common surgical approach, with neck dissection usually performed in cases with clinically apparent positive neck nodes. Radioiodine therapy was frequently applied (54%), although there is no consensus about its benefits. The mean 5- and 10-year overall survival was 91% and 76%, respectively. CONCLUSION: This review serves to further elucidate the main characteristics of this malignancy. HCC of the thyroid is rare and most often presents with a relatively large nodule, whereas lymph node metastases are rare. Given the rarity of HCC, a consensus on their treatment is needed, as doubts remain concerning the role of specific tumor findings and their influence on management.

Transoral endoscopic vestibular approach for thyroidectomy and parathyroidectomy - From promise to practice.

OBJECTIVES: To describe the evolution and recent series on transoral endoscopic vestibular approach thyroidectomy and parathyroidectomy (TOET/PVA). DATA SOURCES: PubMed, Google Scholar. REVIEW METHODS: Review of the available English literature. RESULTS: TOET/PVA may offer several advantages over other remote access thyroidectomy approaches and has been adopted by many centers worldwide with excellent success rates. Indications include benign disease and early thyroid cancer patients. Complication rate is comparable to the trans-cervical approach. The suggested framework has been validated in recent studies and its feasibility confirmed. CONCLUSION: TOET/PVA has now been used to treat thousands of patients worldwide due to low cost, short learning curve and excellent cosmetic outcomes. Further studies will be necessary to demonstrate oncologic non-inferiority and also the true value that is added by the approach.

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.

Occlusion of the internal jugular vein in differentiated thyroid carcinoma: Causes and diagnosis.

Occlusion of the internal jugular vein (IJV) can be observed in thyroid cancer either on preoperative imaging with ultrasound or cross-sectional imaging, particularly contrast-enhanced CT-scan, and can be detected during follow-up when using these same imaging modalities. For thyroid cancer, four different causes of occlusion of the IJV can be identified: venous thrombosis associated with a hypercoagulable state, tumor thrombus in the vein, compression or invasion of the IJV by thyroid disease or lymph node metastases, and fibrotic collapse of the IJV following lateral neck dissection. Clinicians managing patients with thyroid cancer need to be aware of and able to diagnose each of these conditions. The overall patient impact and appropriate management of each will be discussed.

Risk factors for carcinoma ex pleomorphic adenoma in patients presenting with recurrence after resection of pleomorphic adenoma.

BACKGROUND: In patients presenting with recurrent pleomorphic adenoma (rPA), clinical evaluation can fail to recognize carcinoma ex PA (cxPA). We aim to identify the risk factors for cxPA. METHODS: This is a single institution retrospective case-control study from 2000 to 2015. CxPA was diagnosed based on surgical pathology. Demographics, clinical, and social histories were collected. RESULTS: A number of 13/106 (12.3%) patients were diagnosed with cxPA, of which only 4/13 (31%) had clinical features suspicious for malignancy. Compared to benign rPA, factors associated with cxPA included age >50 (odds ratio [OR] 6.67, 95% confidence interval [CI]: 1.71-25.98, P < .01), >10 pack-years of smoking history (OR 3.36, 95% CI: 1.01-11.14, P = .04), and the largest tumor being >2 cm on pathology (OR 4.42, 95% CI: 1.14-17.10, P = .03). CONCLUSIONS: In patients presenting with rPA, risk factors for malignant transformation include age >50, significant smoking history, and tumors larger than 2 cm. Clinical signs of malignancy such as rapid growth or pain are not always present.

Risk factors for subsequent recurrence after surgical treatment of recurrent pleomorphic adenoma of the parotid gland.

BACKGROUND: Recurrent pleomorphic adenoma (PA) can be a lifelong disease, and rates of subsequent recurrence are high. METHODS: Patients between 2000 and 2015 were identified. Primary outcome was subsequent recurrence after surgical salvage. RESULTS: Twenty-seven of 84 patients developed a subsequent recurrence. Risk factors for subsequent recurrence included a higher number of previous recurrences (P < .01), worse preoperative facial nerve function (P < .01), and deep parotid lesion(s) (P < .01). Interval since last surgery was protective (P < .01), specifically >10 years since last surgery (P < .01). For patients with a >10-year interval since their last surgery, the subsequent recurrence-free rate at 10 years follow-up was 80.2% vs 31.8%. CONCLUSIONS: For patients presenting with a >10-year interval since their last surgery, subsequent recurrence rates are low, which may allow for as needed surveillance recommendations. For patients presenting with recurrent PA and ≤10 years since their last surgery, a closer surveillance is warranted.

Prognostic role of intraparotid lymph node metastasis in primary parotid cancer: Systematic review.

BACKGROUND: The prognostic importance of intraparotid lymph node metastasis (P+) in patients with primary parotid gland carcinoma is unclear. METHODS: Nineteen retrospective and noncomparative cohort studies, published between 1992 and 2020, met the inclusion criteria and included 2202 patients for this systematic review. RESULTS: The pooled prevalence of the P in adult patients in the unselected studies was 24.10% (95% confidence interval = 17.95-30.25). The number of P+ lymph nodes per patient was counted in only three studies and ranged from 1 to 11. The 5-year recurrence-free survival rate based on Kaplan-Meier analysis varied from 83% to 88% in P- patients compared to 36% to 54% in P+ patients. The average hazard ratio for tumor recurrence in patients with P+ compared to P- was 2.67 ± 0.58. CONCLUSIONS: P+ is an independent negative prognostic factor in primary parotid gland cancer and should be included into the treatment planning.

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.

Case for staged thyroidectomy.

Recent modifications in the management of well-differentiated thyroid cancer have resulted in significant alterations in clinical approach. Utilizing a series of preoperative and postoperative risk factors involving both the patient and the disease pathology, we offer the term "staged thyroidectomy" to help organize these risk factors for patients and the endocrine team to optimize management. This approach is intended to incorporate our latest nuanced understanding of certain endocrine pathology and may serve to optimize patient outcomes.

Papillary Thyroid Cancer-Aggressive Variants and Impact on Management: A Narrative Review.

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.

Incidence of Occult Lymph Node Metastasis in Primary Larynx Squamous Cell Carcinoma, by Subsite, T Classification and Neck Level: A Systematic Review.

BACKGROUND: Larynx cancer is a common site for tumors of the upper aerodigestive tract. In cases with a clinically negative neck, the indications for an elective neck treatment are still debated. The objective is to define the prevalence of occult metastasis based on the subsite of the primary tumor, T classification and neck node levels involved. METHODS: All studies included provided the rate of occult metastases in cN0 larynx squamous cell carcinoma patients. The main outcome was the incidence of occult metastasis. The pooled incidence was calculated with random effects analysis. RESULTS: 36 studies with 3803 patients fulfilled the criteria. The incidence of lymph node metastases for supraglottic and glottic tumors was 19.9% (95% CI 16.4-23.4) and 8.0% (95% CI 2.7-13.3), respectively. The incidence of occult metastasis for level I, level IV and level V was 2.4% (95% CI 0-6.1%), 2.0% (95% CI 0.9-3.1) and 0.4% (95% CI 0-1.0%), respectively. For all tumors, the incidence for sublevel IIB was 0.5% (95% CI 0-1.3). CONCLUSIONS: The incidence of occult lymph node metastasis is higher in supraglottic and T3-4 tumors. Level I and V and sublevel IIB should not be routinely included in the elective neck treatment of cN0 laryngeal cancer and, in addition, level IV should not be routinely included in cases of supraglottic tumors.

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.

Thyroid Surgery: Whose Domain Is It?

In the United States of America (US), most departments of otorhinolaryngology head and neck surgery have been performing thyroid surgery for many years. In contrast to the US, thyroid surgery is still dominated by general surgeons in most European countries. In numerous university centers, there continues to be friction regarding thyroid surgery. The focus of this editorial is to demonstrate that there is objective data in the literature to suggest that otorhinolaryngologists with appropriate training in head and neck surgery are well suited to perform the entire spectrum of thyroid surgery. The question of who is qualified to perform thyroid surgery is not determined by the basic specialty certification of the surgeon-general or otolaryngology; rather it depends on the training, skill and experience in surgery of the neck, of post-surgical and post-irradiated necks, and of neighboring structures.

Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx Squamous Cell Carcinoma.

PURPOSE: The purpose of this study was to determine if dose de-escalation from 60 to 66 Gy to 30 to 36 Gy of adjuvant radiotherapy (RT) for selected patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma could maintain historical rates for disease control while reducing toxicity and preserving swallow function and quality of life (QOL). PATIENTS AND METHODS: MC1273 was a single-arm phase II trial testing an aggressive course of RT de-escalation after surgery. Eligibility criteria included patients with p16-positive oropharyngeal squamous cell carcinoma, smoking history of 10 pack-years or less, and negative margins. Cohort A (intermediate risk) received 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks along with 15 mg/m2 docetaxel once per week. Cohort B included patients with extranodal extension who received the same treatment plus a simultaneous integrated boost to nodal levels with extranodal extension to 36 Gy in 1.8-Gy fractions twice per day. The primary end point was locoregional tumor control at 2 years. Secondary end points included 2-year progression-free survival, overall survival, toxicity, swallow function, and patient-reported QOL. RESULTS: Accrual was from September 2013 to June 2016 (N = 80; cohort A, n = 37; cohort B, n = 43). Median follow-up was 36 months, with a minimum follow-up of 25 months. The 2-year locoregional tumor control rate was 96.2%, with progression-free survival of 91.1% and overall survival of 98.7%. Rates of grade 3 or worse toxicity at pre-RT and 1 and 2 years post-RT were 2.5%, 0%, and 0%. Swallowing function improved slightly between pre-RT and 12 months post-RT, with one patient requiring temporary feeding tube placement. CONCLUSION: Aggressive RT de-escalation resulted in locoregional tumor control rates comparable to historical controls, low toxicity, and little decrement in swallowing function or QOL.