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Thyroid Cancer: Clinical Diagnosis and Treatment

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (25 December 2025) | Viewed by 16392

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Dr. Alfred A. Simental

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Division of Otolaryngology, Loma Linda University Health, Loma Linda, CA 92354, USA
Interests: thyroid cancer; thyroid and parathyroid surgery
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Special Issue Information

Dear Colleagues,

Thyroid disease and nodules are exceedingly common, and technology has led the forefront in the recent evaluation, diagnosis, and management of thyroid nodules. Ultrasound has largely been responsible for this wave, but new research and the application of molecular analysis and cytopathology education have streamlined the evaluation of thyroid nodules. Long-term follow-up of thyroid cancer has also allowed clinicians and researchers to accurately predict which patients are best treated conservatively and which are treated more aggressively. While techniques such as radiofrequency ablation have offered some opportunity for nodule management, surgery remains the mainstay of the treatment of thyroid cancer. This may range from simple lobectomy to advanced resection of the laryngeal, esophageal, and tracheal structures with acceptable outcomes. We wish to provide the reader with an institutional overview of current diagnosis and management techniques.

Dr. Alfred A. Simental
Guest Editor

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Keywords

thyroid nodule
thyroid ultrasound
radiofrequency ablation
molecular analysis
thyroid surgery

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Related Special Issue

Thyroid Cancer: Diagnosis, Surgical Treatment and Postoperative Radioactive Iodine Therapy: 2nd Edition in Journal of Clinical Medicine

Published Papers (8 papers)

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Research

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12 pages, 629 KB

Open AccessArticle

Recovery Takes Time: Loss of Signal Predicts Delayed Recovery of Vocal Cord Function After Thyroidectomy

by Laura Guglielmetti, Sina Schmidt, Jasmin Al-Hammoud, Moritz Senne, Mirjam Busch, Joachim Wagner, Simone Harsch, Andreas Zielke and Constantin Smaxwil

J. Clin. Med. 2026, 15(10), 3844; https://doi.org/10.3390/jcm15103844 - 16 May 2026

Viewed by 396

Abstract

Background: Post-thyroidectomy vocal cord dysfunction (PT-VCD) is an important side effect of thyroid surgery. With the introduction of intraoperative neuromonitoring (IONM), hopes have been raised that either the rate or severity of PT-VCD could be reduced. However, data to support these concepts are scarce. To better understand the relationship between IONM outcomes and the severity of PT-VCD, a detailed time-course evaluation of recovery of PT-VCD was performed in a continuous clinical quality registry from a specialized high-volume endocrine surgery center. Methods: Data were prospectively recorded in a single-center clinical quality assurance registry (June 2015 to May 2016) and subsequently analyzed retrospectively, with a 12-month follow-up for all cases. All patients underwent vocal cord (VC) laryngoscopy (VCL) by independent ear–nose–throat (ENT) specialists before and after surgery. Cases with newly diagnosed PT-VCD were enrolled in a detailed follow-up program (recruitment from June 2015 to May 2016) that included structured telephone interviews every 4–6 weeks to assess the exact time course of PT-VCD recovery and VC status for a period of at least 12 months. Clinical data were analyzed for variables affecting the time course of recovery by univariate analysis. Results: From 6/2015 to 5/2016 there were 1097 consecutive thyroid procedures. During this period, 78 cases of PT-VCD (1591 nerves at risk (NARs); 4.9%) were entered into the detailed follow-up-program. Of these, three cases of PT-VCD persisted at 12 months (PT-VCD 0.18% NAR), with six cases lost to follow-up (maximum rate of potentially persistent PT-VCD of 0.54% NAR). In total, 15% of PT-VCD cases recovered within 4 weeks; the mean recovery time was 4.4 months, and 6 months after thyroidectomy, 18% still had impaired VCL tests. Individual cases were followed >12 months showing late full recovery of PT-VCD, thereby challenging the definition of permanent VCD. Logistic regression analysis revealed non-transitory loss of signal (ntLOS) (OR for recovery within 12 weeks: 0.39; 95%CI 0.15–0.98; p = 0.046) and more specifically, secondary ntLOS, to be a significant independent predictor of PT-VCP recovery beyond 12 weeks (OR for recovery within 12 weeks 0.303; 95%CI 0.115–0.797; p = 0.016). Conclusions: For the first time, these data provide a detailed description of the time course of PT-VCD recovery in a large cohort, along with correlations to operative data and IONM findings. Our study indicates that recovery from PT-VCD can be prolonged, and specifically, the occurrence of ntLOS—especially secondary ntLOS—during IONM was predictive of a longer recovery trajectory. This suggests that IONM may offer an additional advantage by functioning as a prognostic tool, helping to identify patients at higher risk for extended recovery periods. Such early identification could enable a more targeted approach, potentially allowing for the earlier initiation of supportive interventions, like speech therapy, in those most likely to benefit from proactive management. Full article

(This article belongs to the Special Issue Thyroid Cancer: Clinical Diagnosis and Treatment)

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13 pages, 693 KB

Open AccessArticle

Beyond Size: Integrating Ultrasonographic Features and FNAB Cytology to Predict Thyroid Malignancy—A Retrospective, Single-Center Study

by Nihal Güngör Tunç, Cengiz Durucu and Orhan Tunc

J. Clin. Med. 2026, 15(2), 419; https://doi.org/10.3390/jcm15020419 - 6 Jan 2026

Viewed by 532

Abstract

Background/Objectives: This study aimed to evaluate the relationship between preoperative clinical, ultrasonographic, and cytologic findings and postoperative histopathology in patients with thyroid nodules, and to determine diagnostic factors associated with malignancy. Materials and Methods: A retrospective analysis was conducted on 100 patients who underwent thyroid surgery between September 2012 and April 2014. Preoperative data—including clinical examination, thyroid function tests, and high-resolution ultrasonography—were compared with fine-needle aspiration biopsy (FNAB) results and final histopathology. Ultrasonographic features (echogenicity, calcification, vascularity, and margin) were analyzed for their association with malignancy. Statistical tests included chi-square, t-test, and correlation analysis (p < 0.05 considered significant). Results: Among 100 patients (79 females, 21 males; mean age 47.5 ± 13.9 years), 29 (29%) had benign and 71 (71%) malignant histopathology. Malignancy was significantly associated with older age (p = 0.025), smaller nodule size (p = 0.019), hypoechogenicity (p = 0.001), microcalcifications (p = 0.014), and irregular margins (p = 0.017). FNAB showed a strong correlation with final histopathology (r = 0.65, p = 0.001). The overall sensitivity and specificity of FNAB were 25.4% and 82.8%, respectively. Conclusions: Hypoechogenicity, microcalcifications, and irregular margins were the most reliable ultrasonographic predictors of malignancy. FNAB remains a highly specific but variably sensitive diagnostic tool, and its accuracy increases when interpreted in conjunction with ultrasonographic findings. Integrating cytology with structured imaging systems such as ACR TI-RADS and Bethesda classification enhances diagnostic precision in thyroid nodule evaluation. Full article

(This article belongs to the Special Issue Thyroid Cancer: Clinical Diagnosis and Treatment)

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14 pages, 1106 KB

Open AccessArticle

Impact of American Thyroid Association’s Revised Cancer Management Guidelines on Thyroid Cancer Incidence Trends: A Retrospective Cohort Study, 2000–2020

by Pierre Fwelo, Natalia I. Heredia, Ruosha Li, Ayrton Bangolo, Vignesh K. Nagesh, Simcha Weissman and Xianglin L. Du

J. Clin. Med. 2025, 14(1), 28; https://doi.org/10.3390/jcm14010028 - 25 Dec 2024

Cited by 3 | Viewed by 3169

Abstract

Background: The past four decades have seen a steady increase in thyroid cancer in the United States (US). This study investigated the impact of the American Thyroid Association (ATA)’s revised cancer management guidelines on thyroid cancer incidence trends and how the trends varied by socioeconomic, histologic, geographic, and racial and ethnic characteristics from 2000 to 2020. Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER) database to identify thyroid cancer cases diagnosed among US patients between 2000 and 2020. We employed joinpoint regression software to fit, assess, and compare thyroid cancer incidence trends over time stratified by socioeconomic status (SES), histologic type, geographic location, and race/ethnicity. Results: Between 2000 and 2009, there was an average annual increase of 5.8% in thyroid cancer incidence (average annual percent change (AAPC): 5.8, p < 0.05). Subsequently, there was a modest rise (AAPC: 1.1, p < 0.05) from 2010 to 2015, followed by a significant annual decrease of 4.8% from 2016 to 2020 (AAPC: −4.8, p < 0.05). The joinpoint regression models identified prominent inflection points around 2009 and 2015, aligning with the years of the ATA’s cancer management revisions. These intricate dynamics in thyroid cancer incidence trends from 2000 to 2020 were shaped by SES and histologic, geographic, and racial/ethnic factors. Conclusions: Thyroid cancer incidence trends over the past two decades can be partially explained by the changes in thyroid cancer screening and management recommendations. These findings underscore the importance of cancer management strategies and highlight the need for targeted interventions to address disparities in thyroid cancer incidence across minority demographic groups. Full article

(This article belongs to the Special Issue Thyroid Cancer: Clinical Diagnosis and Treatment)

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Review

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12 pages, 269 KB

Open AccessReview

Synchronous Multiple Parathyroid Carcinoma: A Challenging Diagnosis Influencing Optimal Primary Treatment—A Literature Review to Guide Clinical Decision-Making

by Emanuela Traini, Andrea Lanzafame, Giulia Carnassale, Giuseppe Daloiso, Niccolò Borghesan, Alejandro Martin Sanchez and Amelia Mattia

J. Clin. Med. 2025, 14(15), 5228; https://doi.org/10.3390/jcm14155228 - 24 Jul 2025

Cited by 2 | Viewed by 1152

Abstract

Synchronous multiple parathyroid carcinoma is a rare condition within the already uncommon landscape of parathyroid malignancies, which comprise less than 1% of sporadic primary hyperparathyroidism cases. To date, only seven cases of synchronous multiple parathyroid carcinoma in sporadic primary hyperparathyroidism have been documented. This exceptional rarity complicates both the diagnostic process and therapeutic decision-making. Clinically, parathyroid carcinoma typically presents as a single mass determining severe symptoms. However, no single clinical, biochemical, or imaging feature allows for definitive preoperative diagnosis. Imaging modalities such as ultrasound and sestamibi scans exhibit variable sensitivity and may overlook multi-gland involvement. Histopathological examination remains the only reliable diagnostic method. Management strategies are also controversial: while some advocate for conservative surgery, en bloc resection is generally recommended for its association with improved local control and disease-free survival. Given the exceptional occurrence of synchronous multiple parathyroid carcinoma, there is a lack of standardized protocols for managing parathyroid carcinoma in cases of synchronous and multiple gland involvement. Early multidisciplinary evaluation and individualized treatment planning are therefore crucial. This review aims to synthesize the presently available knowledge about synchronous multiple parathyroid carcinoma, assist clinicians with the limited data available, and discuss the main challenges in the management of this rare entity. Full article

(This article belongs to the Special Issue Thyroid Cancer: Clinical Diagnosis and Treatment)

19 pages, 298 KB

Open AccessReview

Mutational Landmarks in Anaplastic Thyroid Cancer: A Perspective of a New Treatment Strategy

by Janice Pakkianathan, Celina R. Yamauchi, Luiza Barseghyan, Joseph Cruz, Alfred A. Simental and Salma Khan

J. Clin. Med. 2025, 14(9), 2898; https://doi.org/10.3390/jcm14092898 - 23 Apr 2025

Cited by 4 | Viewed by 5016

Abstract

Anaplastic thyroid carcinoma (ATC) is the rarest and most aggressive form of thyroid cancer, marked by a poor prognosis and resistance to conventional treatments. Like many malignancies, ATC has a complex genetic landscape, with numerous mutations driving tumor initiation, progression, and therapeutic resistance. However, recent advances in molecular research have expanded our understanding of these genetic alterations, paving the way for new targeted treatment strategies. Currently, therapies targeting specific genetic mutations, such as BRAF and MEK, show promise, but their effectiveness is limited to patients harboring these mutations. To explore broader therapeutic possibilities, we conducted a comprehensive literature review using the PubMed database and Google to identify studies on key genetic mutations in ATC. By leveraging these molecular insights, we aim to highlight potential therapeutic avenues that could enhance treatment options and improve patient outcomes. Full article

(This article belongs to the Special Issue Thyroid Cancer: Clinical Diagnosis and Treatment)

12 pages, 906 KB

Open AccessReview

The Unappreciated Value of a Cheap, ‘Good Enough’ Method of Detecting Thyroid Cancer

by Salvatore Sciacchitano, Massimo Rugge and Armando Bartolazzi

J. Clin. Med. 2024, 13(23), 7290; https://doi.org/10.3390/jcm13237290 - 30 Nov 2024

Cited by 2 | Viewed by 1832

Abstract

The advent of advanced molecular diagnostic techniques has revealed plenty of information about signaling pathways and gene regulation in cancer, as well as new inputs for the classification of cancer subtypes, diagnosis, prognosis, and prediction of response to therapy. However, in most cases we do not have single biomarkers yet and, therefore, the final diagnosis is often rendered by the combination of multiple results by means of complex algorithms, eventually leading to an increase in their costs. The problem of the costs of such tests is particularly relevant in the case of thyroid cancer (TC), because of the observed increase in the number of patients affected by thyroid nodules (TN)s, in what is considered a global pandemic. High-income countries can afford the cost of the advanced molecular tests for such a multitude of TNs, since they are covered by private insurances. People living in upper-middle, lower-middle, and especially in low-income countries, where the costs for these advanced molecular tests are supported by general taxation and out-of-pocket payments, are exposed as a personal financial burden. Immunohistochemistry in cancer management represents an extremely cost-effective method in different clinical scenarios. In the preoperative recognition of TC, the use of such method, based on Galectin-3 and others protein markers, such as HMBE1, proved to be effective in diagnosing TC in TNs indeterminate at conventional cytology (Bethesda classification III or IV), with an extremely low cost. Moreover, Galectin-3 fulfills one of the major criteria of an ideal marker, being involved in the thyroid cell transformation. Despite this evidence, Galectin-3 ThyroTest is not considered and not even mentioned in many reviews, focused on the appropriate identification of TC, as well as in studies where the cost-effectiveness of the different approaches is comparatively evaluated. The aim of this review is to emphasize the value of the Galectin-3 based immunohistochemistry as a cheap and “good enough” method in the preoperative diagnosis of TC especially in, but not limited to, low-middle income countries. Full article

(This article belongs to the Special Issue Thyroid Cancer: Clinical Diagnosis and Treatment)

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Other

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8 pages, 2402 KB

Open AccessCase Report

Metastatic Medullary Thyroid Carcinoma Without Identifiable Primary Tumor Within the Thyroid Gland, Presenting with Initial Lymph Node Metastasis Followed by Distant Peritoneal Metastasis: A Case Report of a Rare Phenomenon

by Eunyeong Lee, Jungsup Byun, Moonsik Kim, Jae-Hui Kim, Ji-Young Park, Jongmin Park and An Na Seo

J. Clin. Med. 2026, 15(7), 2733; https://doi.org/10.3390/jcm15072733 - 4 Apr 2026

Viewed by 403

Abstract

Background: We report a rare case of a metastatic neoplasm in the regional lymph nodes and peritoneum whose histopathologic and immunophenotypic profiles were most consistent with a diagnosis of medullary thyroid carcinoma (MTC), although a primary tumor was not histologically demonstrated in the thyroidectomy specimen. Case presentation: A 64-year-old man presented with abdominal pain and was found to have increased calcitonin level and a 20 mm lesion in the peritoneum. Peritoneum biopsy revealed plasmacytoid tumor cells which were positive for calcitonin and synaptophysin staining. The patient had a past history of neck dissection due to left side neck mass. The histology revealed metastatic carcinoma with a nested pattern surrounded by fibrous stroma with stromal amyloid deposition. With immunohistochemistry, the findings were most consistent with metastatic MTC, but following total thyroidectomy showed no malignancy. Next-generation sequencing identified a pathogenic HRAS mutation, but RET mutation was not identified. Despite vandetanib treatment, the disease progressed and the patient expired. Conclusions: This case highlights a rare presentation of a metastatic neoplasm highly suggestive of RET wild-type MTC with peritoneal involvement, despite the absence of an identifiable primary lesion. Full article

(This article belongs to the Special Issue Thyroid Cancer: Clinical Diagnosis and Treatment)

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13 pages, 571 KB

Open AccessEditor’s ChoiceSystematic Review

The Efficacy and Safety of Anlotinib in the Treatment of Thyroid Cancer: A Systematic Review

by Calin Muntean, Adelaida Solomon, Remus Calin Cipaian, Razvan Constantin Vonica, Anca Butuca, Vasile Gaborean, Ionut Flaviu Faur and Catalin Vladut Ionut Feier

J. Clin. Med. 2025, 14(2), 338; https://doi.org/10.3390/jcm14020338 - 8 Jan 2025

Cited by 8 | Viewed by 2936

Abstract

Background and Objectives: Anlotinib, a novel multi-kinase inhibitor targeting angiogenesis and tumor proliferation pathways, has shown promising efficacy in various cancers. Its role in treating thyroid cancer, particularly radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC), medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC), is of significant clinical interest. This systematic review aims to evaluate the efficacy and safety of Anlotinib in patients with thyroid cancer, analyzing outcomes such as progression-free survival (PFS), overall survival (OS), response rates, and adverse events. Methods: A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases up to October 2023. The review included randomized controlled trials and prospective studies assessing Anlotinib in thyroid cancer patients. Data extraction and quality assessment were performed independently by two reviewers following PRISMA guidelines. Results: Six studies involving a total of 277 patients were included. In patients with RAIR-DTC, Anlotinib demonstrated significant improvement in median PFS and objective response rates. In advanced or metastatic MTC, Anlotinib significantly prolonged median PFS compared to placebo, with high objective response rates. Subgroup analyses showed that older patients and those with bone metastases benefited significantly from Anlotinib treatment. In patients with ATC, Anlotinib-based chemotherapy yielded a 60% objective response rate. Anlotinib was also effective as neoadjuvant therapy in locally advanced thyroid cancer, achieving an objective response rate of 76.9%. Common adverse events included hypertension, proteinuria, and palmar–plantar erythrodysesthesia syndrome, which were generally manageable. Conclusions: Anlotinib appears to be an effective and well-tolerated treatment option for patients with various types of thyroid cancer, providing significant improvements in PFS and objective response rates. Further large-scale randomized studies are warranted to confirm these findings and to explore long-term outcomes. Full article

(This article belongs to the Special Issue Thyroid Cancer: Clinical Diagnosis and Treatment)

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