Metastasis to the Thyroid Gland: A Critical Review.

BACKGROUND: Metastasis to the thyroid gland from nonthyroid sites is an uncommon clinical presentation in surgical practice. The aim of this review was to assess its incidence management and outcomes. METHODS: A literature review was performed to identify reports of metastases to the thyroid gland. Both clinical and autopsy series were included. RESULTS: Metastases to the gland may be discovered at the time of diagnosis of the primary tumor, after preoperative investigation of a neck mass, or on histologic examination of a thyroidectomy specimen. The most common primary tumors in autopsy studies are from the lung. In clinical series, renal cell carcinoma is most common. For patients with widespread metastases in the setting of an aggressive malignancy, surgery is rarely indicated. However, when patients present with an isolated metastasis diagnosed during follow-up of indolent disease, surgery may achieve control of the central neck and even long-term cure. Other prognosticators include features of the primary tumor, time interval between initial diagnosis and metastasis, and extrathyroid extent of disease. CONCLUSIONS: In patients with thyroid metastases, communication among clinicians treating the thyroid and the index primary tumor is essential. The setting is complex, and decisions must be made considering the features of the primary tumor, overall burden of metastases, and comorbidities. Careful balancing of these factors influences individualized approaches.

Mammary analog secretory carcinoma, low-grade salivary duct carcinoma, and mimickers: a comparative study.

Mammary analog secretory carcinoma (MASC) is a recently recognized low-grade salivary carcinoma characterized by a specific ETV6 rearrangement. We describe 14 new MASCs and examine their immunophenotypic and genetic profiles in the context of look-alikes, namely, low-and high-grade salivary duct carcinoma and acinic cell carcinoma. ETV6 rearrangement, and robust expression of mammaglobin and S100, were demonstrated in 11/11, 14/14, and 12/14 MASCs, respectively. All low-grade salivary duct carcinomas coexpressed S100/mammaglobin (6/6); none harbored ETV6 rearrangements (0/5). Given that S100/mammaglobin coexpression and absence of zymogen granules are features of both MASC and low-grade salivary duct carcinoma, these two are best distinguished histologically. The former is predominantly an extraductal neoplasm with bubbly pink cytoplasm, whereas the latter is a distinct intraductal micropapillary and cribriform process. Querying ETV6 gene status may be necessary for difficult cases. No acinic cell carcinoma expressed mammaglobin (0/13) or harbored an ETV6 rearrangement (0/7); only 1/13 acinic cell carcinomas weakly expressed S100. DOG1 expression was limited or absent among all tumor types, except acinic cell carcinoma which expressed DOG1 diffusely in a canalicular pattern. Therefore, histology and immunohistochemistry (mammaglobin, S100, DOG1) suffices in distinguishing acinic cell carcinoma from both MASC and low-grade salivary duct carcinoma. HER2 (ERBB2) amplification was detected in only 1/10 acinic cell carcinomas, but none of the MASCs or low-grade salivary duct carcinomas tested. High-grade salivary duct carcinomas frequently expressed mammaglobin (11/18) and harbored HER2 amplifications (13/15); none harbored ETV6 rearrangements (0/12). High-grade salivary duct carcinomas can easily be distinguished from these other entities by histology and HER2 amplification.

The Mount Sinai clinical pathway for the management of pheochromocytoma.

OBJECTIVE: Pheochromocytomas are complex tumors that require a comprehensive and systematic management plan orchestrated by a multidisciplinary team. METHODS: To achieve these ends, The Mount Sinai Adrenal Center hosted an interdisciplinary retreat where experts in adrenal disorders assembled with the aim of developing a clinical pathway for the management of pheochromocytomas. RESULTS: The result was a consensus for the diagnosis, perioperative management, and postoperative management of pheochromocytomas, with specific recommendations from our team of adrenal experts, as well as a review of the current literature. CONCLUSION: Our clinical pathway can be applied by other institutions directly or may serve as a guide for institution-specific management.

Neuromonitoring in thyroidectomy: a meta-analysis of effectiveness from randomized controlled trials.

Neuromonitoring in thyroid surgery has been employed to make nerve identification easier and decrease the rates of laryngeal nerve injuries. Several individual randomized controlled trials (RCTs) have been published, which did not identify statistical differences in the rates of recurrent laryngeal nerve (RLN) or external branch of the superior laryngeal nerve (EBSLN) injuries. The objective of this report is to perform meta-analysis of the combined results of individual studies to measure the frequency of RLN and EBSLN injuries in patients who underwent thyroidectomy with routine neuromonitoring in comparison with common practice of search and identification. RCTs comparing routine neuromonitoring versus no use in patients who underwent elective partial or total thyroidectomy were evaluated. Outcomes measured were temporary and definitive palsy of the RLN and EBSLN. A systematic review and meta-analysis was done using random effects model. GRADE was used to classify quality of evidence. Six studies with 1,602 patients and 3,064 nerves at risk were identified. Methodological quality assessment showed high risk of bias in most items. Funnel plot did not reveal publication bias. The risk difference for temporary RLN palsy, definitive RLN palsy, temporary EBSLN palsy, and definitive EBSLN palsy were -2% (95% confidence interval -5.1 to 1); 0% (-1 to 1); -9% (-15 to -2) and -1% (-4 to 2), respectively. Quality was rated low or very low in most outcomes due to methodological flaws. Meta-analysis did not demonstrate a statistically significant decrease in the risk of temporary or definitive RLN injury and definitive EBSLN injury with the use of neuromonitoring. The neuromonitoring group had a statistically significant decrease in the risk of temporary EBSLN injury.

Neuromonitoring of the laryngeal nerves in thyroid surgery: a critical appraisal of the literature.

One of the most significant complication of thyroid surgery is injury of the recurrent laryngeal nerve. Injury of the external branch of the superior laryngeal nerve is a less obvious but occasionally significant problem. Recently, neuromonitoring during thyroidectomy has received considerable attention because of literature encouraging its use, but there is no consensus about its advantages and utility. A critical assessment of the literature on neuromonitoring was conducted in order to define its effectiveness, safety, cost-effectiveness and medical-legal impact. Available data does not show results superior to those obtained by traditional anatomical methods of nerve identification during thyroid surgery. Data about cost-effectiveness is scarce. The literature shows inconsistencies in methodology, patient selection and randomization in various published studies which may confound the conclusions of individual investigations. The current recommendation for use in "high risk" patients should be assessed because definition heterogeneity makes identification of these patients difficult. As routine use of neuromonitoring varies according to geography, its use should not be considered to be the standard of care.

Management of Recurrent Well-Differentiated Thyroid Carcinoma in the Neck: A Comprehensive Review.

Surgery has been historically the preferred primary treatment for patients with well-differentiated thyroid carcinoma and for selected locoregional recurrences. Adjuvant therapy with radioactive iodine is typically recommended for patients with an intermediate to high risk of recurrence. Despite these treatments, locally advanced disease and locoregional relapses are not infrequent. These patients have a prolonged overall survival that may result in long periods of active disease and the possibility of requiring subsequent treatments. Recently, many new options have emerged as salvage therapies. This review offers a comprehensive discussion and considerations regarding surgery, active surveillance, radioactive iodine therapy, ultrasonography-guided percutaneous ablation, external beam radiotherapy, and systemic therapy for well-differentiated thyroid cancer based on relevant publications and current reference guidelines. We feel that the surgical member of the thyroid cancer management team is empowered by being aware and facile with all management options.

The surgical management of renal hyperparathyroidism.

Secondary and tertiary hyperparathyroidism (HPT) develop in patients with renal failure due to a variety of mechanisms including increased phosphorus and fibroblast growth factor 23 (FGF23), and decreased calcium and 1,25-dihydroxy vitamin D levels. Patients present with various bone disorders, cardiovascular disease, and typical laboratory abnormalities. Medical treatment consists of controlling hyperphosphatemia, vitamin D/analog and calcium administration, and calcimimetic agents. Improved medical therapies have led to a decrease in the use of parathyroidectomy (PTX). The surgical indications include parathyroid hormone (PTH) levels >800 pg/ml associated with hypercalcemia and/or hyperphosphatemia despite medical therapy. Other indications include calciphylaxis, fractures, bone pain or pruritis. Transplant recipients often show decreased PTH, calcium and phosphorus levels, but some will have persistent HPT. Evidence suggests that PTX may cause deterioration in renal graft function in the short-term calling into the question the indications for PTX in these patients. Pre-operative imaging is only occasionally helpful except in re-operative PTX. Operative approaches include subtotal PTX, total PTX with or without autotransplantation, and possible thymectomy. Each approach has its proponents, advantages and disadvantages which are discussed. Intraoperative PTH monitoring has a high positive predictive value of cure but a poor negative predictive value and therefore is of limited utility. Hypocalcemia is the most common complication requiring aggressive calcium administration. Benefits of surgery may include improved survival, bone mineral density and alleviation of symptoms.

Primary hyperparathyroidism: Disease of diverse genetic, symptomatic, and biochemical phenotypes.

Genetic, symptomatic, and biochemical heterogeneity of patients with primary hyperparathyroidism (PHPT) has become apparent in recent years. An in-depth, evidence-based review of the phenotypes of PHPT was conducted. This review was intended to provide the resulting information to surgeons who operate on patients with hyperparathyroidism. This review revealed that the once relatively clear distinction between familial and sporadic PHPT has become more challenging by the finding of various germline mutations in patients with seemingly sporadic PHPT. On the one hand, the genetic and clinical characteristics of some syndromes in which PHPT is an important component are now better understood. On the other hand, knowledge is emerging about novel syndromes, such as the rare multiple endocrine neoplasia type IV (MEN4), in which PHPT occurs frequently. It also revealed that, currently, the classical array of symptoms of PHPT is seen rarely upon initial presentation for evaluation. More common are nonspecific, nonclassical symptoms and signs of PHPT. In areas of the world where serum calcium levels are checked routinely, most patients today are "asymptomatic" and they are diagnosed after an incidental finding of hypercalcemia; however, some of them have subclinical involvement of bones and kidneys, which is demonstrated on radiographs, ultrasound, and modern imaging techniques. Last, the review points out that there are three distinct biochemical phenotypes of PHPT. The classical phenotype in which calcium and parathyroid hormone levels are both elevated, and other disease presentations in which the serum levels of calcium or intact parathyroid hormone are normal. Today several, distinct phenotypes of the disease can be identified, and they have implications in the diagnostic evaluation and treatment of patients, as well as possible screening of relatives.

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.

Thyroid and parathyroid surgery in pregnancy.

The consideration of surgery during pregnancy requires weighing the benefit of urgent surgery against the risk to mother and fetus. Surgery during pregnancy involves an increase in both maternal and fetal risks. Thyroid and parathyroid surgery involves physiological risks to both mother and fetus specific to the disease and function of these endocrine glands. Evaluation of a thyroid mass is similar in pregnant patients with ultrasound and fine-needle aspiration biopsy providing the most important information, while the use of radiographic imaging is severely constrained except when specifically required. In general, thyroid surgery can be delayed until after delivery except in cases of airway compromise or aggressive cancer. In contrast, parathyroid surgery is recommended during pregnancy to avoid adverse effects to the neonate.

Contemporary management of cancer of the oral cavity.

Oral cancer represents a common entity comprising a third of all head and neck malignant tumors. The options for curative treatment of oral cavity cancer have not changed significantly in the last three decades; however, the work up, the approach to surveillance, and the options for reconstruction have evolved significantly. Because of the profound functional and cosmetic importance of the oral cavity, management of oral cavity cancers requires a thorough understanding of disease progression, approaches to management and options for reconstruction. The purpose of this review is to discuss the most current management options for oral cavity cancers.

Hepatitis C Virus Infection of Human Thyrocytes: Metabolic, Hormonal, and Immunological Implications.

CONTEXT: Hepatitis C virus (HCV) infection is a prevalent disease worldwide. Thyroid dysfunction is one of the most common extrahepatic manifestations of HCV infection. We hypothesized that HCV can directly infect human thyrocytes thereby causing thyroid dysfunction. SETTING: Human thyrocytes in primary cell culture, ML-1 human thyroid cell line, and Huh7.5 human hepatocyte cell line were infected with HCV using the Huh7.5JFH1 cell line that releases infectious HCV virions. After infection, the release of new virions, production of proinflammatory cytokines, and expression of miR-122 were evaluated. Ribonucleic acid (RNA) extracted from HCV-infected cells and mock-infected cells was subjected to RNA sequencing and transcriptomic analysis. Ingenuity pathway analysis was used to detect up- and down-regulated pathways. RESULTS: Human thyrocytes express major HCV entry factors including CD81, occludin, claudin-1, and scavenger receptor class B1. Viral infection of thyroid cells was confirmed by detection of HCV core protein in supernatants and negative-sense HCV RNA in cell lysates. HCV infection of thyrocytes induced the production of the chemokine CXCL-8 and the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and significantly increased the expression of miR-122. Moreover, HCV infection of thyrocytes decreased expression of the thyroid peroxidase and thyroglobulin genes and increased expression of the deiodinase 2 gene. The top upregulated pathways in HCV-infected thyrocytes were immune pathways and metabolic pathways, while infected hepatocytes upregulated lipid and glucose metabolism pathways as previously reported. CONCLUSIONS: HCV infection may induce thyroid dysfunction by different mechanisms including direct infection of thyrocytes leading to activation of inflammatory pathways and upregulation of miR-122. These findings support a general mechanism for viral induction of autoimmunity through direct infection of target tissues.

Parathyroid cancer: An update.

Parathyroid cancer (PC) is a rare malignant tumor which comprises 0.5-5% of patients with primary hyperparathyroidism (PHPT). Most of these cancers are sporadic, although it may also occur as a feature of various genetic syndromes including hyperparathyroidism-jaw tumor syndrome (HPT-JT) and multiple endocrine neoplasia (MEN) types 1 and 2A. Although PC is characterized by high levels of serum ionized calcium (Ca) and parathyroid hormone (PTH), the challenge to the clinician is to distinguish PC from the far more common entities of parathyroid adenoma (PA) or hyperplasia, as there are no specific clinical, biochemical, or radiological characteristic of PC. Complete surgical resection is the only known curative treatment for PC with the surgical approach during initial surgery strongly influencing the outcome. In order to avoid local recurrence, the lesion must be removed en-bloc with clear margins. PC has high recurrence rates of up to 50% but with favorable long-term survival rates (10-year overall survival of 60-70%) due to its slow-growing nature. Most patients die not from tumor burden directly but from uncontrolled severe hypercalcemia. In this article we have updated the information on PC by reviewing the literature over the past 10 years and summarizing the findings of the largest series published in this period.

Methodological Quality of Systematic Reviews of Intraoperative Neuromonitoring in Thyroidectomy: A Systematic Review.

Importance: Systematic reviews and meta-analyses are considered the best evidence for clinical decision making. Many reviews of intraoperative neuromonitoring (IONM) in thyroidectomy have conflicting results, owing in large part to methodological quality. Objective: To assess the methodological quality and the causes of heterogeneous results of systematic reviews that compare routine IONM vs visual identification of the recurrent laryngeal nerve (RLN) in patients undergoing thyroidectomy. Data Sources: A systematic search was performed of MEDLINE (PubMed), Embase, the Cochrane Library, LILACS (Literatura Latino Americana e do Caribe em Ciências da Saúde), Web of Science, and Google from January 1, 1968, through June 30, 2018. Data were analyzed from July 17 to November 30, 2018. Study Selection: Studies that mentioned performance of a systematic review/meta-analysis during the search period. Data Extraction and Synthesis: Data including study characteristics, type of patients, numbers of nerves at risk, and temporary and definitive RLN paralysis by group were extracted. Data about methodological characteristics, type of statistical analysis and summary estimator, endorsement of systematic review/meta-analysis guidelines, heterogeneity, publication bias, funding, conflict of interest, and statistical analysis were also recorded. The methodological quality was measured with the AMSTAR2 (A Measurement Tool to Assess Systematic Reviews) tool by 2 independent evaluators. Main Outcomes and Measures: Methodological quality. Results: The search identified 13 systematic reviews that included patients who underwent open or minimally invasive thyroidectomy, second operations, and a mixture of low- and high-risk procedures. The mean compliance with the AMSTAR2 overall criteria was 53% (range, 11%-83%); with critical criteria, 71% (range, 50%-94%). The percentage of nerves at risk from RCTs was 4.8%. The mean (SD) crude rate of definitive RLN paralysis was 0.81% (0.22%; median, 0.75% [range, 0.53%-1.30%]) in the monitoring group and 1.14% (0.56%; median, 0.96% [range, 0.57%-2.56%]) in the control group. Conclusions and Relevance: A substantial number of systematic reviews of IONM in thyroidectomy have conflicting results, but their mean methodological quality is critically low. Design of a systematic review should comply with methodological standards and recommendations to offer relevant and practical information for decision making.