Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study.

BACKGROUND: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. METHODS: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. FINDINGS: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). INTERPRETATION: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. FUNDING: None.

Cribriform adenocarcinoma of the minor salivary glands: a case report.

BACKGROUND: Polymorphous adenocarcinoma is the third most common malignant salivary gland tumor. Within polymorphous adenocarcinoma, cribriform adenocarcinoma of salivary glands is a rare subtype and resembles papillary thyroid carcinoma histopathologically. Diagnostically, cribriform adenocarcinoma of salivary glands is challenging for pathologists and surgeons alike as initial presentation and cytologic nuclear features can be easily confused with papillary thyroid carcinoma arising from a thyroglossal duct remnant or lingual thyroid. CASE PRESENTATION: A healthy 64-year-old Caucasian woman presented to a community otolaryngologist with a 4-year history of progressive postnasal drip, globus sensation, and eventual dysphonia. Flexible fiberoptic laryngoscopy showed a large, smooth, vallecular lesion filling the oropharynx. Computed tomography imaging of the neck showed a rounded heterogeneous mass centered within the right aspect of the oropharynx measuring 4.2 × 4.4 × 4.5 cm. Fine needle aspiration biopsy was suspicious for papillary carcinoma due to microscopic findings of malignant cells, nuclear grooves, and a powdery chromatin pattern. In the operating room, the tumor was resected en bloc using a lateral pharyngotomy approach with partial resection of the right lateral hyoid. A limited cervical lymphadenectomy was performed to facilitate the lateral pharyngotomy approach and two out of three lymph nodes demonstrated regional metastatic disease. Nuclear grooves, nuclear membrane notching, and occasional intranuclear pseudoinclusions were identified, which are overlapping histopathological characteristics of papillary thyroid carcinoma and cribriform adenocarcinoma of salivary glands. It was negative for thyroglobulin and thyroid transcription factor-1, which was in keeping with cribriform adenocarcinoma of salivary glands rather than papillary thyroid carcinoma. CONCLUSION: It is difficult to distinguish cribriform adenocarcinoma of salivary glands from papillary thyroid carcinoma solely by cytology, and the distinct characteristics of regional lymph node metastasis coupled with nuanced histologic differences should be emphasized in the evaluation of patients presenting with neck lymphadenopathy and an unknown primary or tongue mass. If sufficient fine needle aspiration biopsy material is available, thyroid transcription factor-1, thyroglobulin, or molecular testing may prove useful in differentiating cribriform adenocarcinoma of salivary glands from papillary thyroid carcinoma. A misdiagnosis of papillary thyroid carcinoma may lead to inappropriate treatment including unnecessary thyroidectomy. Therefore, it is critical for both pathologists and surgeons to be aware of this uncommon entity to avoid misdiagnosis and subsequent mismanagement.

Lenvatinib-induced hypocalcaemia due to transient primary hypoparathyroidism.

CONTEXT: Radioiodine refractory differentiated thyroid cancer can be effectively treated with multi-tyrosine-kinase inhibitors (MKIs). Hypocalcaemia has been reported among the side effects of these drugs, but little is known about its pathophysiology and clinical relevance. CASE REPORT: We report the case of a 78-years-old woman with an aggressive papillary thyroid cancer infiltrating perithyroidal structures. The extent of surgery was limited to hemithyroidectomy, RAI treatment could not be performed, and she started lenvatinib treatment. After 4 months of therapy, the patient accessed the Emergency Department for a grade III hypocalcaemia (corrected serum calcium: 6.6 mg/dL, n.v. 8.1-10.4 mg/dL), due to primary hypoparathyroidism (serum PTH: 12.6 ng/L, n.v. 13-64 ng/L). The patient was treated with intravenous calcium infusions and vitamin D supplementation. After discharge, the oral dose of carbonate calcium (CaCO3) was of 6 g/day, and was titrated according to blood exams. Two weeks after discharge, while taking CaCO3 at the dose of 3 g/day, the patient experienced symptomatic grade II hypercalcemia (corrected serum calcium: 11.6 mg/dL), associated to the spontaneous reprise of PTH secretion, and leading to oral calcium withdrawal. During the subsequent follow-up, the patient remained eucalcemic without calcium supplementation. CONCLUSIONS: Though hypocalcaemia has been described as potential side effect of MKI treatment, this is the first report of a lenvatinib-induced primary hypoparathyroidism, in a patient with a documented normal parathyroid function after surgery. The periodical assessment of calcium-phosphorus metabolism is thus warranted to prevent this potentially lethal side effect, in both post-surgical hypoparathyroid and euparathyroid patients.

Simultaneous unilateral laparoscopic adrenalectomy for pheochromocytoma and thyroidectomy in MEN 2A and MEN 2B syndrome.

Not required for Clinical Vignette.

Primary thyroid squamous cell carcinoma presenting as a left-sided neck lump.

The elderly patient presenting with a neck lump often raises concerns regarding a malignancy. Thyroid gland malignancies are well recognised and subtype characteristics thoroughly researched, whereas rarer types of thyroid carcinoma are reported infrequently and often behave more aggressively. An 83-year-old woman was referred from the general practitioner (GP) to otolaryngology due to a 7-month history of an unexplained enlarging left-sided neck swelling. A fine-needle aspiration revealed cytology consistent with squamous cell carcinoma (SCC). Staging imaging failed to reveal evidence of a primary foci elsewhere. The definitive diagnosis was that of a primary thyroid SCC: a rare entity with limited citations in the literature. Surgical resection has been found to comprise the optimal treatment for this disease. Recognition of the possibility of primary thyroid SCC in elderly patients presenting with a neck lump, with prompt referral to a head and neck specialist permits a timely progression to potentially curative surgical management, a more promising prognosis and reduced mortality rates.

Concomitant malignancies in the neck: follicular dendritic cell sarcoma; a rare tumour presenting as a right-sided neck nodal mass and papillary carcinoma thyroid.

Follicular dendritic cell sarcoma is a rare low-grade sarcoma of mesenchymal origin. It involves the lymph nodes more commonly and rarely extranodal sites. The most common lymph node is cervical and usually presents as a painless asymptomatic mass. More often, it is a misdiagnosis, and there is a delay in treatment. It is rarely associated with Castleman disease, myasthenia gravis. Diagnosis of this condition is by histopathology and immunochemistry. Surgery is the primary modality of treatment, and adjuvant therapy has been tried with no definite trials due to the rarity of the disease. Here, we report a case of concomitant follicular dendritic sarcoma of the right cervical lymph node and papillary carcinoma of the thyroid managed in our institute. There was a line of investigations approaching towards a diagnosis, and she underwent total thyroidectomy and right modified radical neck dissection.

Thyroid cancer surgery during the coronavirus disease 2019 pandemic: perioperative management and oncological and anatomical considerations.

The coronavirus disease 2019 (COVID-19) pandemic has changed many aspects of our everyday lives and medical practice, including oncology treatment; thyroid cancer surgery is not an exception. The reported number of fine-needle aspirations performed during the first semester of 2020 was significantly reduced. Poorly differentiated, medullary and anaplastic thyroid tumors are considered important indications for immediate surgical intervention. By contrast, most well-differentiated carcinomas present slow growth, and thus surgery can be deferred for a short period of time during which patients are under active surveillance. Thyroid surgeries have decreased during the COVID-19 pandemic. Furthermore, prior to any intervention, negative COVID-19 status - with the use of a nasopharyngeal swab and reverse transcription PCR assay as the gold standard and chest CT scan as a complementary modality in some cases - must be confirmed to achieve a COVID-free pathway. Thorough preoperative assessment regarding both oncological and anatomical aspects should be performed to identify optimal timing for safe management.

Thyroid surgery during the COVID-19 pandemic: results from a systematic review.

PURPOSE: During the COVID-19 pandemic, elective thyroid surgery is experiencing delays. The problem is that the COVID-19 pandemic is ongoing. The research purposes were to systematically collect the literature data on the characteristics of those thyroid operations performed and to assess the safety/risks associated with thyroid surgery during the COVID-19 pandemic. METHODS: We used all the procedures consistent with the PRISMA guidelines. A comprehensive literature in MEDLINE (PubMed) and Scopus was made using ''Thyroid'' and "coronavirus" as search terms. RESULTS: Of a total of 293 articles identified, 9 studies met the inclusion criteria. The total number of patients undergoing thyroid surgery was 2217. The indication for surgery was malignancy in 1347 cases (60.8%). Screening protocols varied depending on hospital protocol and maximum levels of personal protection equipment were adopted. The hospital length of stay was 2-3 days. Total thyroidectomy was chosen for 1557 patients (1557/1868, 83.4%), of which 596 procedures (596/1558, 38.3%) were combined with lymph node dissections. Cross-infections were registered in 14 cases (14/721, 1.9%), of which three (3/721, 0.4%) with severe pulmonary complications of COVID-19. 377 patients (377/1868, 20.2%) had complications after surgery, of which 285 (285/377, 75.6%) hypoparathyroidism and 71 (71/377, 18.8%) recurrent laryngeal nerve injury. CONCLUSION: The risk of SARS-CoV-2 transmission after thyroid surgery is relatively low. Our study could promote the restart of planned thyroid surgery due to COVID-19. Future studies are warranted to obtain more solid data about the risk of complications after thyroid surgery during the COVID-19 era.

Thyroid surgery during coronavirus-19 pandemic phases I, II and III: lessons learned in China, South Korea, Iran and Italy.

OBJECTIVE: We compared demographic and clinic-pathological variables related to the number of surgeries for thyroid conditions or for cancer, morbidity, and fine needle aspiration (FNA) practices among Covid19 pandemic phases I, II, III and the same seasonal periods in 2019. METHODS: The prospective database of the Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Changchun, China was used for this study. Covid19 emergency levels were stratified according to the World Health Organization: phase I (January 25-February 25, 2020), phase II (February 26-March 19), phase III (March 20-April 20). RESULTS: There were fewer outpatient FNAs and surgeries in 2020 than in 2019. There were no thyroid surgeries during phase I. There were also fewer surgeries for cancer with a significant reduction of advanced stage cancer treatments, mainly stage T1b N1a in phase II and T3bN1b in phase III. Operative times and postoperative stays were significantly shorter during the pandemic compared to our institutional baseline. In phase III, vocal cord paralysis (VCP) increased to 4.3% of our baseline numbers (P = 0.001). There were no cases of Covid19-related complications during the perioperative period. No patients required re-admission to the hospital. CONCLUSION: The Covid19 outbreak reduced thyroid surgery patient volumes. The decrease of Covid19 emergency plans contributed to unexpected outcomes (reduction of early stage cancer treatment, decreased operative times and hospital stays, increased VCP rate).

North East London coronavirus disease 2019 protocol for diagnostics in two-week wait head and neck cancer patients.

BACKGROUND: The coronavirus disease 2019 pandemic requires urgent modification to existing head and neck cancer diagnosis and management practices. A protocol was established that utilises risk stratification, early investigation prior to clinical review and a reduction in aerosol generating procedures to lessen the risk of coronavirus disease 2019 spread. METHODS: Two-week wait referrals were stratified into low, intermediate and high risk. Low risk patients were referred back to primary care with advice; intermediate and high risk patients underwent investigation. Clinical encounters and aerosol generating procedures were minimised. A combined diagnostic and therapeutic surgical approach was undertaken where possible. RESULTS: Forty-one patients were used to assess feasibility. Thirty-one per cent were low risk, 35 per cent were intermediate and 33 per cent were high risk. Thirty-three per cent were discharged with no imaging. CONCLUSION: Implementing this protocol reduces the future burden on tertiary services, by empowering primary care physicians to re-refer low risk patients. The protocol is applicable across the UK and avoids diagnostic delay.

Endocrine surgery during COVID-19 pandemic: do we need an update of indications in Italy?

The ongoing spread of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a significant threat to global health. As the coronavirus outbreak began spreading, hospitals were forced to relocate resources to treat the growing number of COVID-19 patients. As a consequence, doctors across the country canceled tens of thousands of nonurgent surgeries. However, recognizing that the COVID-19 situation may be highly variable and fluid in different communities across the country, elective surgery could be still allowed in some centers for patients included in the high-priority class. The majority of endocrine disorders requiring surgical treatment in patients identifiable as first-priority class, or needing hospitalization within 30 days, are generally represented by malignant thyroid tumors, hyperthyroidism, hyperparathyroidism, and some adrenal disorders. The need for urgent intervention is evaluated on a case-by-case basis according to the severity of the symptoms, the likelihood of progression, and global clinical judgment. On the basis of the above indications, during the last 4 weeks, we performed 18 planned surgical treatments in patients with thyroid cancer (total thyroidectomies, plus lymph node dissection if needed) or multinodular toxic goiter. In no case, postoperative ventilatory support was needed, and the average hospital stay was 3 days. The negative COVID-19 status for all the treated patients was appropriately evaluated beforehand. Nobody knows how long the current COVID-19 pandemic will be lasting. Certainly, we will be requested in the next future to incrementally offer surgical services for endocrine disorders that have been deferred for the COVID-19 pandemic.