Medicine › Endocrinology, Diabetes and Metabolism

Thyroid Cancer Diagnosis and Treatment

Works Count: 85051

Wikipedia

Description

This cluster of papers focuses on the management, diagnosis, and molecular genetics of thyroid cancer, including differentiated and medullary thyroid carcinoma. It covers topics such as the management guidelines for thyroid nodules, the role of BRAF mutation in papillary thyroid carcinoma, ultrasound imaging for thyroid nodules, and the use of radioactive iodine therapy. The cluster also discusses the molecular pathogenesis and genetic alterations associated with thyroid cancer.

Keywords

Thyroid Nodules; Differentiated Thyroid Cancer; Management Guidelines; Thyroid Carcinoma; BRAF Mutation; Ultrasound; Radioactive Iodine Therapy; Molecular Genetics; Medullary Thyroid Cancer; Fine-Needle Aspiration

Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma

2015-03-27

Samuel A. Wells , L. Sylvia , Henning Dralle +7 more

The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association.

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Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989.

1993-12-01

Ian Hay , Erik J. Bergstralh , John R. Goellner +2 more

Integrated Genomic Characterization of Papillary Thyroid Carcinoma

2014-10-01

Nishant Agrawal , Rehan Akbani , Bülent Arman Aksoy +7 more

<h2>Summary</h2> Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here, we describe the genomic landscape of 496 PTCs. We observed a low frequency of somatic alterations … <h2>Summary</h2> Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here, we describe the genomic landscape of 496 PTCs. We observed a low frequency of somatic alterations (relative to other carcinomas) and extended the set of known PTC driver alterations to include <i>EIF1AX</i>, <i>PPM1D</i>, and <i>CHEK2</i> and diverse gene fusions. These discoveries reduced the fraction of PTC cases with unknown oncogenic driver from 25% to 3.5%. Combined analyses of genomic variants, gene expression, and methylation demonstrated that different driver groups lead to different pathologies with distinct signaling and differentiation characteristics. Similarly, we identified distinct molecular subgroups of <i>BRAF</i>-mutant tumors, and multidimensional analyses highlighted a potential involvement of oncomiRs in less-differentiated subgroups. Our results propose a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties, which has the potential to improve their pathological classification and better inform the management of the disease.

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High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma.

2003-04-01

Edna Teruko Kimura , Marina N. Nikiforova , Zhaowen Zhu +3 more

Thyroid papillary cancers (PTCs) are associated with activating mutations of genes coding for RET or TRK tyrosine kinase receptors, as well as of RAS genes. Activating mutations of BRAF were … Thyroid papillary cancers (PTCs) are associated with activating mutations of genes coding for RET or TRK tyrosine kinase receptors, as well as of RAS genes. Activating mutations of BRAF were reported recently in most melanomas and a small proportion of colorectal tumors. Here we show that a somatic mutation of BRAF, V599E, is the most common genetic change in PTCs (28 of 78; 35.8%). BRAF(V599E) mutations were unique to PTCs, and not found in any of the other types of differentiated follicular neoplasms arising from the same cell type (0 of 46). Moreover, there was no overlap between PTC with RET/PTC, BRAF, or RAS mutations, which altogether were present in 66% of cases. The lack of concordance for these mutations was highly unlikely to be a chance occurrence. Because these signaling proteins function along the same pathway in thyroid cells, this represents a unique paradigm of human tumorigenesis through mutation of three signaling effectors lying in tandem.

Guidelines for the management of thyroid cancer

2014-07-01

Petros Perros , Kristien Boelaert , Steve Colley +7 more

In spite of advances in diagnostic methods, surgical techniques and clinical care, there are differences in survival of patients with thyroid cancer in different countries, and the outcome in the … In spite of advances in diagnostic methods, surgical techniques and clinical care, there are differences in survival of patients with thyroid cancer in different countries, and the outcome in the UK prior to 1989 appeared to be worse than in other western European nations.1 The reasons for this are unclear and may be multifactorial. There is a sense that outcomes in the UK are improving, but only long term national registry data can confirm or refute this in future. However, it may not be unreasonable to speculate that the impact of previous editions of these guidelines, and recent changes in cancer services within the National Health Service may have contributed. These include mandatory specialist multidisciplinary team management of all cancers (http://www.mycancertreatment.nhs.uk/wp-content/themes/mct/uploads/2012/09/resources_measures_HeadNeck_Measures_April2011.pdf), regular mandatory national peer review, equity of access to specialist care, the cancer drug fund, national cancer research groups supporting trials, patient support groups, national audits by professional organisations, the cancer reform strategy and survivorship programme. It is hoped that the third edition of the national guidelines for thyroid cancer, and their implementation through local protocols of the NHS networks, will continue to facilitate this process and improve care and outcomes in the UK. The intention is to provide guidance for all those involved in the management of patients with differentiated thyroid cancer (DTC) and some of the rarer thyroid cancers. This document is not intended as guidelines for management of thyroid nodules, though the role of ultrasound (US) in assessing thyroid nodules is included. A summary of the key recommendations for the management of adult differentiated thyroid cancer, medullary thyroid cancer (MTC) and anaplastic thyroid cancer is provided (see previous section). Randomised trials are often not available in this setting. Therefore, evidence is based on large retrospective studies and the level of evidence is ascribed according to the Scottish Intercollegiate Guidelines Network 50 (A guideline developer's handbook (http://www.sign.ac.uk/pdf/sign50.pdf). These guidelines do not address thyroid lymphomas or metastases to the thyroid. In the period 1971–1995, the annual UK incidence was reported at 2.3 per 100 000 women and 0.9 per 100 000 men, with approximately 900 new cases and 250 deaths recorded in England and Wales due to thyroid cancer every year.2 In 2010, data from Cancer Research UK indicate 2654 new cases in the UK and 346 deaths. (http://www.cancerresearchuk.org/cancer-info/cancerstats/types/thyroid/uk-thyroid-cancer-statistics). Annual incidence data for the UK from 2008 show 5.1 per 100 000 women and 1.9 per 100 000 men (http://www.cancerresearchuk.org/cancer-info/cancerstats/types/thyroid/uk-thyroid-cancer-statistics). Thyroid cancer is the most common malignant endocrine tumour, but represents only about 1% of all malignancies.2 The incidence of thyroid cancer is increasing globally, mostly due to PTC,3 including in the paediatric population.4 The bulk of the increase is lower stage cancers and/or incidental micro-papillary thyroid cancers found when surgery is performed for thyroid diseases other than cancer.5, 6 Overall mortality from thyroid cancer has remained stable over many years.7 It has been suggested that the increase in incidence of thyroid cancer is due to better detection of incidental microcarcinomas.7, 8 This view has been challenged by studies which found that the incidence of thyroid cancers of all sizes has been increasing over time.3, 9 It seems plausible that factors other than increased detection, may underlie the rising incidence of thyroid cancer, and may include changing iodine status and exposure to radiation,10 but in most cases the cause is unknown. Nuclear fallout is a well recognised cause of an increase in the risk of thyroid cancer in children. Following the Chernobyl accident, the incidence of thyroid cancer rose several hundred times in children in the region. Therapeutic and diagnostic X-rays in childhood are also possible causes of thyroid cancer in adults; exposure to these sources should be limited whenever possible. In cases of populations or individuals being contaminated with 131I the thyroid can be protected by administering potassium iodide.11-13 At present there is no screening programme to detect thyroid cancer for the general population. Screening is possible for familial MTCs associated with specific oncogene mutations. The genetic basis of papillary, follicular and anaplastic thyroid cancer has been investigated and the roles and potential prognostic value of several genes, e.g. RET, TRK, RAS, BRAF, PPARG and p53, have been identified. Testing for these genes is not routinely available in clinical practice.14 Patients should be informed about and given the opportunity to consider participation in ongoing randomized clinical trials in cases where there is genuine clinical equipoise or lack of level 1 evidence (4, D). Key recommendation The long-term outcome of patients treated effectively for differentiated thyroid cancer (DTC) is usually favourable. The overall 10-year survival rate for middle-aged adults with DTC is 80–90%. However, 5–20% of patients develop local or regional recurrences and 10–15% distant metastases.1-3 Nine per cent of patients with a diagnosis of thyroid cancer die of their disease.4, 5 It is important to assess both risk of death from the disease and risk of recurrence in patients with DTC using a prognostic scoring system. This enables a more accurate prognosis to be given and the appropriate treatment decisions to be made. Several factors have been shown consistently to be important for predicting death and recurrence in multivariate analyses of large patient cohorts: Age at the time of diagnosis is one of the most consistent prognostic factors in patients with DTC. The risk of recurrence and death increases with age, particularly after the age of 40 years.6-11 Young children, under the age of 10 years, are at higher risk of recurrence than older children or adolescents.12-15 The male gender has been reported as an independent risk factor in some but not all studies.4, 9, 10, 14, 15 The prognosis of papillary thyroid carcinoma (PTC) is better than that of follicular thyroid cancer (FTC). However, if the confounding effects of age and extent of tumour at diagnosis are removed, survival rates are comparable.6, 9, 17-19 Within the PTC group, poorer prognosis is associated with specific histological types (e.g. tall cell, columnar cell)20-24 and the degree of cellular differentiation and vascular invasion.7, 25 'Widely invasive' and 'vascular invasion' are features of follicular cancers associated with a poorer prognosis.26 Poorly differentiated and oncocytic follicular (Hürthle-cell) carcinomas are also associated with a poorer outcome.9, 10, 27, 28, 14, 29 The risk of recurrence and mortality correlates with the size of the primary tumour.6, 8-11, 16, 27 Extra-thyroidal invasion,6, 8-11, 25, 30, 31 lymph node metastases,6, 9, 10, 27, 32 and distant metastases25, 33-35 are all important prognostic factors.14 Several staging systems have been proposed for DTC and continue to evolve.36, 37 Any of these systems can be used to assign patients to the high-risk or low-risk group (MACIS is used only for PTC), based on well-established prognostic factors (detailed below), but TNM and MACIS probably yield the most useful prognostic information.38, 39 The TNM classification is used extensively for registration and predicts mortality (Table 2.1) (for online calculator see: http://www.thyroid.org/thyroid-cancer-staging-calculator/). From the clinical standpoint, the objective is to tailor treatment to the individual so as to minimise the risk of death and recurrence. Equally important, is avoidance of unnecessary exposure of patients with a good prognosis to invasive therapies associated with long-term side effects, which may impact on quality of life. The principles of personalised medicine are increasingly being applied to the management of patients with thyroid cancer. Advances in molecular medicine and the development of prognostic nomograms40 will facilitate this process. However, for the foreseeable future, conventional clinical and histopathological parameters remain the principal tools on which management decisions have to be based. The scoring and prognostic systems described above are helpful in stratifying patients, though they have evolved not only for clinical management but also for design and analysis of clinical trials or retrospective clinical studies and for cancer registration purposes.41 Post-operative TNM staging predicts the risk of death from disease, and is a valuable indicator of overall prognosis (Table 2.1). However, it does not take into account individual responses to treatment, which may alter prognosis, and it does not predict recurrence. A three tier system adapted from the American Thyroid Association (ATA) guidelines48 may be used to assign risk for persistent or recurrent disease (Table 2.2). This is useful for determining whether patients should undergo radioiodine remnant ablation (RRA) (Chapter 9), and the intensity and method of follow up in the post-operative setting. For patients who have undergone total thyroidectomy with R0 resection and RRA, the 9–12 months post-RRA stimulated thyroglobulin (sTg), whole body scan (WBS) (if performed) and neck ultrasound (US), will allow potential modification of the initial static risk estimate based on the patient's response to RRA. Using a combination of clinicopathological factors with treatment response criteria allows a more personalised approach to treatment, follow up and prognostication49 (Table 2.3). This will facilitate follow up as the majority of patients will have achieved an excellent response and TSH suppression can be relaxed (Chapter 11), allowing the TSH concentration to rise to the low-normal range. Annual Tg assessment can be carried out without stimulation and follow up intervals can be extended (Chapter 13). The TNM classification (7th edition)47 (Table 2.1) is recommended38, 43-45 (4, D). Key recommendation The ATA post-operative risk stratification for risk of recurrence shown in Table 2.2 is recommended (adapted from48) (4, C). Key recommendation Allocation to one of three response groups after Dynamic Risk Stratification (Table 2.3) is recommended (2-, C). Key recommendation Clear recommendations for or against treatments are possible for specific patient groups, but in many cases there is uncertainty. Both clinicians and patients can feel uncomfortable dealing with uncertainty. However, if handled appropriately, this process can become a positive experience and increase confidence about making the right choice. To achieve this, patient and clinician need to have adequate time for discussion, the opportunity for relatives or other third parties to participate in the discussion should be given if desired by the patient, time to reflect should be allowed, good quality information about the implications of the different options should be made available, and the responsible clinician should lead and guide the patient' choice using his/her expert knowledge. When the evidence for or against a treatment is inconclusive and no well designed, peer reviewed randomised or prospective national or institutional studies are ongoing to address this issue or if available, declined by the patient, these guidelines recommend a personalised approach to decision making (Personalised Decision Making) (4, D). Key recommendation Personalised Decision Making involves clinicians and patients working together to find a solution, that best suits the circumstances of the individual patient. This process consists of: Examples of uncertainty in decision making where Personalised Decision Making may be applied are shown in Table 2.4. MicroPTC with any of the following (Chapter 8.2): PTC <1 cm who have no clinical / radiological evidence of lymph node involvement, but have any of the following characteristics (Chapter 7.6): Thyroid nodules are common in adults and may be detected by palpation in 3–7% of patients.1 The prevalence may be as high as 70% or more if sensitive imaging such as ultrasonography is used (Chapter 4). The vast majority of thyroid nodules are benign and do not require urgent referral. Furthermore, thyroid cancer is uncommon in patients who are not euthyroid, and assessment of biochemical thyroid status is useful in deciding on the referral pathway by the general practitioner (GP) (Chapter 21). Referrals for suspected cancer are required to be seen in secondary care within 2 weeks, as set out in the Department of Health Cancer Plan document, Cancer waiting targets: a guide.2 Specialists in secondary care have a maximum of 31 days from 'decision to treat' to first definitive treatment and a maximum of 62 days from urgent GP referral for suspected cancer to first definitive treatment (Fig. 3.1). In the case of thyroid nodules, the time of 'decision to treat' is when a decision to proceed to thyroidectomy is made after discussion with the patient. Decisions to treat thyroid cancers should follow multidisciplinary team (MDT) discussions, in accordance with the measures of the National Cancer Peer Review Programme.3 The date of first definitive treatment is the date of thyroidectomy (either hemithyroidectomy or total thyroidectomy). The most common presentation of thyroid cancer is a newly discovered thyroid nodule or increase in size of a pre-existing nodule. However, the vast majority of patients (95%) presenting in this manner have benign disease. Furthermore the prognosis of those who harbour a malignancy is generally excellent. Thyroid nodules and goitre are common and often noted coincidentally when patients are being imaged for other reasons. The vast majority (95%) of cases have benign disease. GPs must exercise common sense in selecting which cases should be referred and with what degree of urgency. Patients with thyroid nodules who may be managed in primary care (4, D): Patients who should be referred non-urgently (4, D): Symptoms needing urgent referral (2-week rule)2 (4, D): Symptoms needing immediate (same day) referral (4, D): Patients should be referred to a surgeon, endocrinologist, or nuclear medicine physician who has a specialist interest in thyroid cancer and is a core member of the MDT. National Cancer Peer Review Programme, measure 11-1D-103i3 Key Recommendation While the decision to proceed with investigations will be appropriate in most cases, there are occasions when no further investigation may be a better choice. Co-morbidities and other factors including patient choice are important in making this judgment. Circumstances where further investigation of thyroid nodules for malignancy may not be in the patient's best interests include: Clinical features which are statistically associated with increased probability of malignancy include: US is an extremely sensitive examination for thyroid nodules. It can be specific for the diagnosis of thyroid carcinoma (particularly papillary carcinoma), and aids decision making about which nodules to perform FNAC. US also consistently increases the yield of diagnostic FNACs (Chapter 4). Good Practice Point ☑ Key recommendation Undergoing investigations for a thyroid lump may be a stressful experience for the patient, exacerbated by inadequate or misleading information and by excessive waiting times for tests. High quality information about the individual's risk of having thyroid cancer and the complexities and limitations of diagnostic tests to exclude thyroid cancer should be provided to patients (4, D). Key recommendation The patient should be informed of the diagnosis of cancer by a member of the MDT in person, preferably in the presence of a nurse during a private, uninterrupted consultation. Patients should be offered the opportunity of having a relative or friend present during the consultation. Facilities should be available for this to be done during a private, uninterrupted consultation (4, D). Key recommendation Sonographically a thyroid nodule is a discrete lesion, distinguishable from the adjacent normal thyroid parenchyma. While thyroid nodules are found on clinical examination in 3–7% of the adult population, the incidence of detectable nodules on ultrasound (US) examination is between 30% and 70% and increases progressively with age.1 While size of the tumour has major consequences in staging and prognosis of thyroid cancer (Chapter 2), the size of a thyroid nodule, correlates poorly with the risk of malignancy. US is an extremely sensitive examination for thyroid nodules. It can be specific for the diagnosis of thyroid carcinoma (particularly papillary carcinoma), and aids decision-making about which nodules to perform fine-needle aspiration cytology (FNAC).2 US also consistently increases the yield of diagnostic FNAC.3 All patients being investigated for possible thyroid cancer should undergo an US of the neck in secondary care by an appropriate, competent practitioner. Good Practice Point ☑ The information derived from US of thyroid nodules should always be interpreted in the context of the individual patient's clinical picture (and when available, cytology findings). Good Practice Point ☑ US features indicative of benign or malignant nodules are described in Table 4.1. No single US feature is diagnostic. Several retrospective series indicate that US characteristics of a nodule can be used reliably to detect malignancy.1, 2, 4 The Kim criteria provide the greatest sensitivity,5 while the American Association of Clinical Endocrinologists guidelines have the highest specificity6, 7 (Table 4.2). The Society of Radiologists in Ultrasound criteria, which rely primarily on size, are least accurate in the prediction of malignancy.1 Multiple operators can achieve concordant results following training in the detection of the relevant signs.2 A graphic presentation of the recognised signs that can be used to classify thyroid nodules is shown in Fig. 4.1. This allows Radiologists to use an US (U) classification (U1–U5). The use of such a classification system for the prediction of malignancy helps to determine whether a FNAC should be performed.3-5, 8, 9 The use of the U1–U5 scoring/grading system is recommended for assessing risk of malignancy and guiding FNAC (2+, C). Key Recommendation Despite size of a nodule being used as a criterion in some guidelines, the evidence does not support size as a reliable indicator of malignancy.5, 8-14 While there are some studies indicating that nodule size is associated with malignancy,15-17 a larger body of evidence suggests that size is not specific in distinguishing benign from malignant thyroid nodules.18-21 Furthermore, guidelines that have used size as a criterion for the differentiating between benign and malignant thyroid nodules, have been shown to lack accuracy, compared to guidelines that use nodule morphology as a criterion.6 Predictive US signs continue to evolve: techniques such as elastography,22 and other new signs can be incorporated easily into the U classification system outlined above. Cystic change is invariably detected within benign nodules however can be seen infrequently, in thyroid malignancy. In solid/cystic nodules, analysis of the internal solid portion should be carried out. Specific signs for malignancy are eccentric location of the solid portion, a non-smooth margin, hypoechogenicity of the solid portion and microcalcification within the solid portion. The overall shape of the nodule ie taller than wide (AP > TR), or irregular overall shape are also relevant for solid/cystic nodules as a predictor of malignancy.23 The high sensitivity of US for the detection of papillary carcinoma can result in the finding of small (<1 cm) nodules that are suspicious for thyroid malignancy. In such cases extra thyroidal extension and associated metastatic lymphadenopathy will influence the decision as to whether or not to perform FNAC. When there is no evidence of extra thyroidal disease, or no associated high risk clinical history, the decision whether or not to perform FNAC will depend on the clinical picture, and the responsible clinician needs to make an appropriate judgment (supported by the MDT) about pursuing cytological confirmation, in order to avoid overtreatment of clinically insignificant micro-papillary thyroid carcinomas (microPTCs).24 US appearances that are indicative of a benign nodule (U1–U2) should be regarded as reassuring not requiring fine needle aspiration cytology (FNAC), unless the patient has a statistically high risk of malignancy (Chapter 3.7) (2++, B). Key Recommendation If the US appearances are equivocal, indeterminate or suspicious of malignancy (U3–U5), an US guided FNAC should follow10 (2++, B). Key Recommendation If a nodule is being assessed by US, the practitioner (be they a sonographer, surgeon, endocrinologist or radiologist) should be competent in identifying the characteristic signs that can allow a differentiation of thyroid nodules (i.e. either benign (U2), equivocal/indeterminate (U3), suspicious (U4) or malignant (U5) as outlined in the U classification, Fig. 4.1. Good Practice Point ☑ A report should identify the various characteristics and give appropriate measurements of significant thyroid nodules/masses and the U score. In multinodular thyroids, the score for the most suspicious nodule should be recorded. Good Practice Point ☑ Any retrosternal extension or tracheal deviation should be noted. Good Practice Point ☑ When a malignancy is suspected a full assessment of the remainder of the neck for associated lymph node metastases is mandatory. Good Practice Point ☑ The follow up of thyroid nodules should depend upon the initial US appearances and associated cytology (Fig. 4.2).25-28 Nodules with Thy2 cytology but indeterminate or suspicious US features should undergo repeat FNAC for confirmation. The rate of malignancy in this setting is significant, and evidence supports repeat cytological sampling28 (2++, B). Key Recommendation Atypical (Thy3a), follicular (Thy3f), suspicious (Thy4) and diagnostic (Thy5) cytology is discussed in Chapter 5. Nodules detected by PET-CT with focal FDG activity should be investigated with ultrasound and FNAC, unless disseminated disease is identified and the prognosis from an alternative malignancy would preclude further investigation (1++, A). Key Recommendation US assessment should be recorded with images captured on picture archiving and communications system (PACS), with a formal written report linked to the Radiology Information System.33 Good Practice Point ☑ Reporting should follow the diagnostic criteria as outlined in Table 4.3. Good Practice Point ☑ Such services should be managed in conjunction with Radiology allowing supervision/advice to be sought when necessary. Good Practice Point ☑ Training should follow the guidance outlined by the Royal College of Radiologists for other non-Radiology groups.33 Good Practice Point ☑ Fine needle aspiration cytology (FNAC) is a valuable and cost-effective pre-operative investigation for thyroid nodules in adults.1-3 The results can reassure that a nodule is benign, triage patients for diagnostic surgery, or provide a definite diagnosis of some thyroid malignancies enabling one-stage therapeutic surgery. FNAC does have drawbacks, however, especially the sometimes high rate of inadequate/unsatisfactory samples; the inability to distinguish between non-neoplastic, benign and malignant follicular lesions1, 4, 5 and the difficulty in detecting follicular variant of papillary thyroid carcinoma.6-12 It is essential that adequate material is obtained for diagnosis and that the microscopy is performed by pathologists experienced in thyroid disease.13, 14 A high quality service requires close co-operation between biomedical/healthcare scientists, pathologists, radiologists/sonographers and clinicians managing the patients so that appropriate procedures are set up, implemented and monitored.13 Aspiration should be performed by an appropriately trained individual with expertise and interest in thyroid disease. They should perform sufficient aspirates to maintain expertise and they should audit their results.15 FNAC samples taken with ultrasound (US) guidance (Chapter 4), have increased accuracy13, 16-18 and reduced rates of unsatisfactory samples.19-22 Immediate assessment of the sample for adequacy by biomedical scientists or pathologists at the time of aspiration can reduce the rate of unsatisfactory samples and be cost-effective especially if the underlying adequacy rate is low,23-27 and facilitate collection of material for ancillary tests. FNAC can also be used in the diagnosis of suspicious lymph nodes and the measurement of thyroglobulin in the washout can improve diagnostic accuracy (Appendix 1).28, 29 Molecular analysis (e.g. BRAF V600E mutation for PTC, alone or part of a panel) is an emerging field and may refine the prediction of both benignity and malignancy in thyroid cytology samples.30-51 All FNAC requests should include full clinical details including a description of the abnormality (diagrams are helpful). Good Practice Point ☑ A nominated pathologist should be a core member of the local thyroid cancer Multidisciplinary Team (MDT).53 National Cancer Peer Review Programme, measure 11-2I-114 Thyroid cytology should be reported by a cytopathologist with experience in such samples and with access to colleagues with additional experience for second opinions when appropriate. Such review increases accuracy of cytology13, 54, 55 (2+, C). Key recommendation There should be routine correlation between the cytological diagnosis and any subsequent histology. Good Practice Point ☑ The cytology report should contain a descriptive section interpreting the findings, followed by the Thy numerical category as defined by RCPath (Section 5.2). Good Practice Point ☑ Key recommendation Numerical categories increase accuracy,56 aid local audit, allow comparison with other centres including internationally, and can guide discussion on further management but are not a replacement for the descriptive interpretation. The clinical scenario should be taken into account when reporting the cytology.1 Good Practice Point ☑ Additional cases (e.g. Thy3 category cytology) can benefit from MDT discussion and this should be at the discretion of the local MDT. Good Practice Point ☑ As noted above (Section 5.1), the Thy numerical diagnostic categories should be used in addition to a full text report. The Royal College of Pathologists publication should be followed for the terminology, and is summarised below. For full explanation of the categories, see the original RCPath document and any subsequent revision.66 These UK categories now map exactly to the Bethesda categories used in the USA67, which facilitates comparison between the two systems. The likelihood of a malignancy on subsequent histology increases with increasing Thy category and should be 100% for Thy5, though rates of 98–99% are reported.68, 69 Suspicious cytology (Thy4) is associated with malignant histology in about 68–70%.69, 70 Follicular or indeterminate cytology (Thy3) is followed by malignant histology in around 9·5–43% of cases70, 9, 71-77, 69 the risk being highest with suspicious ultrasound features.75 There is a false negative rate for benign (Thy2) cytology results (usually <3%).62 Malignancy can be found in nodules with Thy1 cytology (4·5–8·5%22, 63), especially if the lesion is cystic (14·3%).89 There is interobserver variation in the interpretation of follicular-patterned lesions in both cytology and histology.78, 69, 79, 80 Subdivision of indeterminate cytology (Thy3) further stratifies the risk of malignancy.8, 81, 8, 82-84, 65, 85, 86 Immunocytochemical and molecular methods may also assist in stratification of risk.87-91 Patients with suspected thyroid cancer should normally be seen in accordance with the national target for urgent referrals (currently 2 weeks) (Chapter 3). Good Practice Point ☑ If there are progressive/severe respiratory problems associated with a thyroid mass, patients must be referred and seen without delay. Good Practice Point ☑ Patients with new onset of stridor and a thyroid mass must be assessed as emergency cases. Good Practice Point ☑ Decisions should be made promptly with respect to diagnosis and treatment (maximum 31 days from diagnosis to first treatment and 62 days from urgent referral to first treatment, Chapter 3, Fig. 3.1). Good Practice Point ☑ The following should be recorded in the medical records: Good Practice Point ☑ There is a strong case for patients with thyroid cancer to be operated on and treated by clinicians who have appropriate training and experience. Complication rates from thyroid surgery are lower when patients, adult and paediatric, are treated by 'high volume' surgeons.1-3 Membership of the British Association of Endocrine and Thyroid Surgeons (BAETS) mandates annual returns and provides comparative performance data on surgical numbers and outcome measures (http://baets.e-dendrite.com). The surgeon should have training and expertise in the management of thyroid cancer and be a core member of the multidisciplinary team (MDT) (Improving outcomes in Head and Neck Cancer http://www.nice.org.uk/nicemedia/live/10897/28851/28851.pdf) Key recommendation Surgeons who operate on patients with thyroid cancer should perform a minimum of 20 thyroidectomies per year National Cancer Peer Review Programme, measure 11-2I-149 Cervical lymph node dissection should be performed by MDT authorised surgeons National Cancer Peer Review Programme, measure 1

Lenvatinib versus Placebo in Radioiodine-Refractory Thyroid Cancer

2015-02-11

Martin Schlumberger , Makoto Tahara , Lori J. Wirth +7 more

Lenvatinib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor α, RET, and KIT, showed … Lenvatinib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor α, RET, and KIT, showed clinical activity in a phase 2 study involving patients with differentiated thyroid cancer that was refractory to radioiodine (iodine-131).In our phase 3, randomized, double-blind, multicenter study involving patients with progressive thyroid cancer that was refractory to iodine-131, we randomly assigned 261 patients to receive lenvatinib (at a daily dose of 24 mg per day in 28-day cycles) and 131 patients to receive placebo. At the time of disease progression, patients in the placebo group could receive open-label lenvatinib. The primary end point was progression-free survival. Secondary end points included the response rate, overall survival, and safety.The median progression-free survival was 18.3 months in the lenvatinib group and 3.6 months in the placebo group (hazard ratio for progression or death, 0.21; 99% confidence interval, 0.14 to 0.31; P<0.001). A progression-free survival benefit associated with lenvatinib was observed in all prespecified subgroups. The response rate was 64.8% in the lenvatinib group (4 complete responses and 165 partial responses) and 1.5% in the placebo group (P<0.001). The median overall survival was not reached in either group. Treatment-related adverse effects of any grade, which occurred in more than 40% of patients in the lenvatinib group, were hypertension (in 67.8% of the patients), diarrhea (in 59.4%), fatigue or asthenia (in 59.0%), decreased appetite (in 50.2%), decreased weight (in 46.4%), and nausea (in 41.0%). Discontinuations of the study drug because of adverse effects occurred in 37 patients who received lenvatinib (14.2%) and 3 patients who received placebo (2.3%). In the lenvatinib group, 6 of 20 deaths that occurred during the treatment period were considered to be drug-related.Lenvatinib, as compared with placebo, was associated with significant improvements in progression-free survival and the response rate among patients with iodine-131-refractory thyroid cancer. Patients who received lenvatinib had more adverse effects. (Funded by Eisai; SELECT ClinicalTrials.gov number, NCT01321554.).

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Medullary Thyroid Cancer: Management Guidelines of the American Thyroid Association

2009-05-26

Richard T. Kloos , Charis Eng , Douglas B. Evans +7 more

Inherited and sporadic medullary thyroid cancer (MTC) is an uncommon and challenging malignancy. The American Thyroid association (ATA) chose to create specific MTC Clinical Guidelines that would bring together and … Inherited and sporadic medullary thyroid cancer (MTC) is an uncommon and challenging malignancy. The American Thyroid association (ATA) chose to create specific MTC Clinical Guidelines that would bring together and update the diverse MTC literature and combine it with evidence-based medicine and the knowledge and experience of a panel of expert clinicians.

A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995

1998-12-15

Scott A. Hundahl , Irvin D. Fleming , Amy M. Fremgen +1 more

BACKGROUND The National Cancer Data Base (NCDB) represents a national electronic registry system now capturing nearly 60% of incident cancers in the U. S. In combination with other Commission on … BACKGROUND The National Cancer Data Base (NCDB) represents a national electronic registry system now capturing nearly 60% of incident cancers in the U. S. In combination with other Commission on Cancer programs, the NCDB offers a working example of voluntary, accurate, cost-effective "outcomes management" on a both a local and national scale. In addition, it is of particular value in capturing clinical information concerning rare cancers, such as those of the thyroid. METHODS For the accession years 1985-1995, NCDB captured demographic, patterns-of-care, stage, treatment, and outcome information for a convenience sample of 53,856 thyroid carcinoma cases (1% of total NCDB cases). This article focuses on overall 10-year relative survival and American Joint Committee on Cancer (AJCC) (3rd/4th edition) stage-stratified 5-year relative survival for each histologic type of thyroid carcinoma. Care patterns also are discussed. RESULTS The 10-year overall relative survival rates for U. S. patients with papillary, follicular, Hürthle cell, medullary, and undifferentiated/anaplastic carcinoma was 93%, 85%, 76%, 75%, and 14%, respectively. For papillary and follicular neoplasms, current AJCC staging failed to discriminate between patients with Stage I and II disease at 5 years. Total thyroidectomy ± lymph node sampling/dissection represented the dominant method of surgical treatment rendered to patients with papillary and follicular neoplasms. Approximately 38% of such patients receive adjuvant iodine-131 ablation/therapy. At 5 years, variation in surgical treatment (i.e., lobectomy vs. more extensive surgery) failed to translate into compelling differences in survival for any subgroup with papillary or follicular carcinoma, but longer follow-up is required to evaluate this. NCDB data appeared to validate the AMES prognostic system, as applied to papillary cases. Younger age appeared to influence prognosis favorably for all thyroid neoplasms, including medullary and undifferentiated/anaplastic carcinoma. NCDB data also revealed that unusual patients diagnosed with undifferentiated/anaplastic carcinoma before age of 45 years have better survival. CONCLUSIONS The NCDB system permits analysis of care patterns and survival for large numbers of contemporaneous U. S. patients with relatively rare neoplasms, such as thyroid carcinoma. In this context, it represents an unsurpassed clinical tool for analyzing care, evaluating prognostic models, generating new hypotheses, and overcoming the volume-related drawbacks inherent in the study of such neoplasms. [See editorial on pages 2434-6, this issue.] Cancer 1998;83:2638-2648. © 1998 American Cancer Society.

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American Association Of Clinical Endocrinologists, Associazione Medici Endocrinologi, And European Thyroid Association Medical Guidelines For Clinical Practice For The Diagnosis And Management Of Thyroid Nodules

2010-05-01

Hossein Gharib , Enrico Papini , Ralf Paschke +7 more

Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Taskforce

2006-02-01

David S. Cooper , Gerard M. Doherty , Bryan R. Haugen +7 more

a. Goals of therapy b.Role of preoperative staging with diagnostic testing c.Surgery for differentiated thyroid cancer iii.Extent of initial surgery iii.Completion thyroidectomy d.Pathological and clinical staging systems e. Postoperative radioiodine … a. Goals of therapy b.Role of preoperative staging with diagnostic testing c.Surgery for differentiated thyroid cancer iii.Extent of initial surgery iii.Completion thyroidectomy d.Pathological and clinical staging systems e. Postoperative radioiodine remnant ablation iii.Modes of thyroid hormone withdrawal iii.Role of diagnostic scanning before ablation iii.Radioiodine ablation dosage iv.Use of recombinant human thyrotropin for remnant ablation iv.Role of low iodine diets vi.Performance of post therapy scans f.Thyroxine suppression therapy g.Role of adjunctive external beam radiation or chemotherapy 5. Differentiated Thyroid Cancer: Long-Term Management . . . . . . . .

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Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer

1994-11-01

Ernest L. Mazzaferri , Sissy Jhiang

The Bethesda System for Reporting Thyroid Cytopathology

2009-10-21

Edmund S. Cibas , Syed Z. Ali

To address terminology and other issues related to thyroid fine-needle aspiration (FNA), the National Cancer Institute (NCI) hosted the NCI Thyroid FNA State of the Science Conference. The conclusions regarding … To address terminology and other issues related to thyroid fine-needle aspiration (FNA), the National Cancer Institute (NCI) hosted the NCI Thyroid FNA State of the Science Conference. The conclusions regarding terminology and morphologic criteria from the NCI meeting led to the Bethesda Thyroid Atlas Project and form the framework for The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). For clarity of communication, TBSRTC recommends that each report begin with 1 of 6 general diagnostic categories. The project participants hope that the adoption of this flexible framework will facilitate communication among cytopathologists, endocrinologists, surgeons, radiologists, and other health care providers; facilitate cytologic-histologic correlation for thyroid diseases; facilitate research into the epidemiology, molecular biology, pathology, and diagnosis of thyroid diseases; and allow easy and reliable sharing of data from different laboratories for national and international collaborative studies.

Increasing Incidence of Thyroid Cancer in the United States, 1973-2002

2006-05-09

Louise Davies , H. Gilbert Welch

Increasing cancer incidence is typically interpreted as an increase in the true occurrence of disease but may also reflect changing pathological criteria or increased diagnostic scrutiny. Changes in the diagnostic … Increasing cancer incidence is typically interpreted as an increase in the true occurrence of disease but may also reflect changing pathological criteria or increased diagnostic scrutiny. Changes in the diagnostic approach to thyroid nodules may have resulted in an increase in the apparent incidence of thyroid cancer.To examine trends in thyroid cancer incidence, histology, size distribution, and mortality in the United States.Retrospective cohort evaluation of patients with thyroid cancer, 1973-2002, using the Surveillance, Epidemiology, and End Results (SEER) program and data on thyroid cancer mortality from the National Vital Statistics System.Thyroid cancer incidence, histology, size distribution, and mortality.The incidence of thyroid cancer increased from 3.6 per 100,000 in 1973 to 8.7 per 100,000 in 2002-a 2.4-fold increase (95% confidence interval [CI], 2.2-2.6; P<.001 for trend). There was no significant change in the incidence of the less common histological types: follicular, medullary, and anaplastic (P>.20 for trend). Virtually the entire increase is attributable to an increase in incidence of papillary thyroid cancer, which increased from 2.7 to 7.7 per 100,000-a 2.9-fold increase (95% CI, 2.6-3.2; P<.001 for trend). Between 1988 (the first year SEER collected data on tumor size) and 2002, 49% (95% CI, 47%-51%) of the increase consisted of cancers measuring 1 cm or smaller; 87% (95% CI, 85%-89%) consisted of cancers measuring 2 cm or smaller. Mortality from thyroid cancer was stable between 1973 and 2002 (approximately 0.5 deaths per 100,000).The increasing incidence of thyroid cancer in the United States is predominantly due to the increased detection of small papillary cancers. These trends, combined with the known existence of a substantial reservoir of subclinical cancer and stable overall mortality, suggest that increasing incidence reflects increased detection of subclinical disease, not an increase in the true occurrence of thyroid cancer.

Fine-Needle Aspiration Biopsy of the Thyroid: An Appraisal

1993-02-15

Hossein Gharib

Objective: To review the literature on the utility of fine-needle aspiration biopsy in the diagnostic management of nodular thyroid disease. Data Sources: Relevant articles published in major English-language medical journals … Objective: To review the literature on the utility of fine-needle aspiration biopsy in the diagnostic management of nodular thyroid disease. Data Sources: Relevant articles published in major English-language medical journals during the last 10 years. Data Extraction: Articles were reviewed to assess the results of fine-needle aspiration biopsy and its effect on thyroid management and cost of care. Data Synthesis: Fine-needle aspiration biopsy of the thyroid gland is safe, inexpensive, minimally invasive, and highly accurate in the diagnosis of nodular thyroid disease. Four cytologic diagnostic categories are used. Rates for these categories, based on data pooled from seven series, were as follows: benign, 69%; suspicious, 10%; malignant, 4%; and nondiagnostic, 17%. Analysis of recent data suggests a false-negative rate of 1% to 11%, a false-positive rate of 1% to 8%, a sensitivity of 65% to 98%, and a specificity of 72% to 100%. Limitations of fine-needle aspiration are related to the skill of the aspirator, the expertise of the cytologist, and the difficulty in distinguishing some benign cellular adenomas from their malignant counterparts. The introduction of fine-needle aspiration has had a substantial effect on the management of patients with thyroid nodules. The percentage of patients undergoing thyroidectomy has decreased by 25%, and the yield of carcinoma in patients who undergo surgery has increased from 15% to at least 30%. Fine-needle aspiration has decreased the cost of care by 25%. Conclusions: Fine-needle aspiration biopsy is safe, accurate, and cost-effective. The procedure has a central role in the management of thyroid nodules and should be used as the initial diagnostic test.

Management of a Solitary Thyroid Nodule

1993-02-25

Jane F. Desforges , Ernest L. Mazzaferri

The solitary thyroid nodule, defined as a palpably discrete swelling within an otherwise apparently normal gland, is usually a benign lesion. However, patient and physician alike are typically concerned about … The solitary thyroid nodule, defined as a palpably discrete swelling within an otherwise apparently normal gland, is usually a benign lesion. However, patient and physician alike are typically concerned about the possibility of thyroid cancer. This review describes a strategy for the treatment of clinically euthyroid patients who have a solitary thyroid nodule that prevents unnecessary testing while identifying the few patients who require therapy. Management has changed in recent years, but important differences of opinion remain over which nodules should be surgically excised. Several recent reviews address these issues comprehensively13.Prevalence of Thyroid Nodules and CancerThe . . .

The Thyroid Nodule

2004-10-20

László Hegedűs

A 42-year-old woman presents with a palpable mass on the left side of her neck. She has no neck pain and no symptoms of thyroid dysfunction. Physical examination reveals a … A 42-year-old woman presents with a palpable mass on the left side of her neck. She has no neck pain and no symptoms of thyroid dysfunction. Physical examination reveals a solitary, mobile thyroid nodule, 2 cm by 3 cm, without lymphadenopathy. The patient has no family history of thyroid disease and no history of external irradiation. Which investigations should be performed? Assuming that the nodule is benign, which, if any, treatment should be recommended?

Long-Term Outcome of 444 Patients with Distant Metastases from Papillary and Follicular Thyroid Carcinoma: Benefits and Limits of Radioiodine Therapy

2006-05-10

Cosimo Durante , Nadia Haddy , E. Baudin +7 more

The goal of this study was to estimate the cumulative activity of (131)I to be administered to patients with distant metastases from thyroid carcinoma.A total of 444 patients were treated … The goal of this study was to estimate the cumulative activity of (131)I to be administered to patients with distant metastases from thyroid carcinoma.A total of 444 patients were treated from 1953-1994 for distant metastases from papillary and follicular thyroid carcinoma: 223 had lung metastases only, 115 had bone metastases only, 82 had both lung and bone metastases, and 24 had metastases at other sites. Treatment consisted of the administration of 3.7 GBq (100 mCi) (131)I after withdrawal of thyroid hormone treatment, every 3-9 months during the first 2 yr and then once a year until the disappearance of any metastatic uptake. Thyroxine treatment was given at suppressive doses between (131)I treatment courses.Negative imaging studies (negative total body (131)I scans and conventional radiographs) were attained in 43% of the 295 patients with (131)I uptake; more frequently in those who were younger, had well-differentiated tumors, and had a limited extent of disease. Most negative studies (96%) were obtained after the administration of 3.7-22 GBq (100-600 mCi). Almost half of negative studies were obtained more than 5 yr after the initiation of the treatment of metastases. Among patients who achieved a negative study, only 7% experienced a subsequent tumor recurrence. Overall survival at 10 yr after initiation of (131)I treatment was 92% in patients who achieved a negative study and 19% in those who did not.(131)I treatment is highly effective in younger patients with (131)I uptake and with small metastases. They should be treated until the disappearance of any uptake or until a cumulative activity of 22 GBq has been administered. In the other patients, other treatment modalities should be used when tumor progression has been documented.

Natural History, Treatment, and Course of Papillary Thyroid Carcinoma*

1990-08-01

Leslie J. DeGroot , Edwin L. Kaplan , Maureen McCormick +1 more

We have analyzed the course of papillary thyroid carcinoma in 269 patients managed at the University of Chicago, with an average follow-up period of 12 yr from the time of … We have analyzed the course of papillary thyroid carcinoma in 269 patients managed at the University of Chicago, with an average follow-up period of 12 yr from the time of diagnosis. Patients were categorized by clinical class; I, with intrathyroidal disease; II, with cervical nodal metastases; III, with extrathyroidal invasion; and IV, with distant metastases. Half of the patients had a history of thyroid enlargement known, on the average, for over 3 yr. In 15% of patients given thyroid hormone, the mass decreased in size. The peak incidence of cancer was when subjects were between 20–40 yr of age. Tumors averaged 2.4 cm in size; 21.6% had tumor capsule invasion, and 46% of patients had multifocal tumors. Sixty-six percent of the patients had near-total or total thyroidectomy. The overall incidence of postoperative hypoparathyroidism was 8.4%, but the incidence was zero in 83 near-total or total thyroidectomies carried out by 1 surgeon. Twenty-five percent of the patients had continuing or recurrent disease, and 8.2% died from cancer. Deaths occurred largely in patients with class III or IV disease. Cervical lymph nodes were associated with increased recurrences, but not increased deaths. Extrathyroidal invasion carried an increased risk of 5.8-fold for death, and distant metastases increased this risk 47-fold. Age over 45 yr at diagnosis increased the risk of death 32-fold. Tumor size over 3 cm increased the risk of death 5.8-fold. Surgical treatment combining lobectomy plus at least contralateral subtotal thyroidectomy was associated, by Cox proportional hazard analysis, with decreased risk of death in patients with tumors larger than 1 cm and decreased risk of recurrence among all patients, including patients in classes I and II, compared to patients who underwent unilateral thyroid surgery or bilateral subtotal resections. By χ2 analysis, 131I ablation of residual thyroid tissue after operation was associated with decreased risk of recurrence in tumors larger than 1 cm and decreased risk of death in patients in classes I and II with tumors more than 1 cm in size. The data strongly support the use of more extensive initial surgery in class I and II patients with tumors more than 1 cm in size as well as postoperative radioactive 131I ablation of thyroid remnant tissue.

Thyroid Incidentalomas: Management Approaches to Nonpalpable Nodules Discovered Incidentally on Thyroid Imaging

1997-02-01

Gerry H. Tan

Background: The introduction of highly sensitive imaging techniques has made it possible to detect many nonpalpable nodules, or “incidentalomas,” in the thyroid. Discovery of these lesions raises concerns about their … Background: The introduction of highly sensitive imaging techniques has made it possible to detect many nonpalpable nodules, or “incidentalomas,” in the thyroid. Discovery of these lesions raises concerns about their malignancy, but the optimal strategy for managing these lesions has not been clearly established. Purpose: To review evidence about incidentalomas, including prevalence and risk for malignancy, and to provide recommendations for their evaluation and treatment. Data Sources: Literature searches for relevant articles published in the past 15 years in major English-language medical journals, review of selected articles published before this period, and reviews of bibliographies in textbooks. Study Selection: Three studies on autopsy findings, 11 studies on ultrasonographic findings, and other reports on nonpalpable thyroid nodules were included. Data Extraction: Data on the prevalence of nodules on autopsy and in ultrasonographic series, palpation compared with ultrasonography, the risk for malignancy in nodules found in irradiated glands, the natural history of thyroid nodules, and the prevalence of occult cancer were collated and reviewed. Data Synthesis: Prevalence of thyroid incidentalomas estimated from autopsy studies ranges from 30% to 60%. Studies comparing clinical palpation with thyroid imaging show a prevalence of 13% to 50%. Prospective studies of randomly selected patients have reported a prevalence of 19% to 67%. The risk for malignancy in asymptomatic nodules found in nonirradiated glands is 0.45% to 13% (mean ±SD, 3.9% ± 4.1%). Conclusions: High-resolution ultrasonography is sensitive and capable of detecting many small, nonpalpable thyroid nodules. Most of these lesions are benign. For most patients with nonpalpable nodules that are incidentally detected by thyroid imaging, simple follow-up neck palpation is sufficient.

Molecular pathogenesis and mechanisms of thyroid cancer

2013-02-22

Mingzhao Xing

Worldwide Increasing Incidence of Thyroid Cancer: Update on Epidemiology and Risk Factors

2013-01-01

Gabriella Pellegriti , Francesco Frasca , Concetto Regalbuto +2 more

Background . In the last decades, thyroid cancer incidence has continuously and sharply increased all over the world. This review analyzes the possible reasons of this increase. Summary . Many … Background . In the last decades, thyroid cancer incidence has continuously and sharply increased all over the world. This review analyzes the possible reasons of this increase. Summary . Many experts believe that the increased incidence of thyroid cancer is apparent, because of the increased detection of small cancers in the preclinical stage. However, a true increase is also possible, as suggested by the observation that large tumors have also increased and gender differences and birth cohort effects are present. Moreover, thyroid cancer mortality, in spite of earlier diagnosis and better treatment, has not decreased but is rather increasing. Therefore, some environmental carcinogens in the industrialized lifestyle may have specifically affected the thyroid. Among potential carcinogens, the increased exposure to medical radiations is the most likely risk factor. Other factors specific for the thyroid like increased iodine intake and increased prevalence of chronic autoimmune thyroiditis cannot be excluded, while other factors like the increasing prevalence of obesity are not specific for the thyroid. Conclusions . The increased incidence of thyroid cancer is most likely due to a combination of an apparent increase due to more sensitive diagnostic procedures and of a true increase, a possible consequence of increased population exposure to radiation and to other still unrecognized carcinogens.

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Current Approaches to Primary Therapy for Papillary and Follicular Thyroid Cancer

2001-03-01

Ernest L. Mazzaferri , Richard T. Kloos

Patient variables Age Ͻ15 yr or Ͼ45 yr Age 15-45 yr Male sex Female sex Family history of thyroid cancer No family history of thyroid cancer Tumor variables Tumor Ͼ4 … Patient variables Age Ͻ15 yr or Ͼ45 yr Age 15-45 yr Male sex Female sex Family history of thyroid cancer No family history of thyroid cancer Tumor variables Tumor Ͼ4 cm in diameter Tumor Ͻ4 cm in diameter Bilateral disease Unilateral disease Extrathyroidal extension No extrathyroidal extension Vascular Invasion (both papillary and follicular thyroid cancer) Absence of vascular invasion Cervical, or mediastinal lymph node metastases No lymph node metastases Certain tumor subtypes: Hu ¨rthle cell, tall cell, columnar cell, diffuse sclerosis, insular variants Encapsulated papillary thyroid carcinoma, papillary microcarcinoma, cystic papillary thyroid carcinoma Marked nuclear atypia, tumor necrosis, and vascular invasion (i.e.histologic grade) Absence of nuclear atypia, tumor necrosis, and vascular invasion Tumors or metastases that concentrate radioiodine poorly or not at all Tumors or metastases that concentrate radioiodine well Distant metastases No distant metastases Modified from the NCCN guidelines for the diagnosis and treatment of thyroid cancer (3, 6).

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New Sonographic Criteria for Recommending Fine-Needle Aspiration Biopsy of Nonpalpable Solid Nodules of the Thyroid

2002-03-01

Eun‐Kyung Kim , Cheong Soo Park , Woung Youn Chung +4 more

The purpose of our study was to provide new sonographic criteria for fine-needle aspiration biopsy of nonpalpable solid thyroid nodules.Sonographic scans of 155 nonpalpable thyroid nodules in 132 patients were … The purpose of our study was to provide new sonographic criteria for fine-needle aspiration biopsy of nonpalpable solid thyroid nodules.Sonographic scans of 155 nonpalpable thyroid nodules in 132 patients were prospectively classified as having positive or negative findings. Sonographic findings that suggested malignancy included microcalcifications, an irregular or microlobulated margin, marked hypoechogenicity, and a shape that was more tall than it was wide. If even one of these sonographic features was present, the nodule was classified as positive (malignant). If a nodule had none of the features described, it was classified as negative (benign). The final diagnosis of a lesion as benign (n = 106) or malignant (n = 49) was confirmed by fine-needle aspiration biopsy and follow-up (>6 months) in 83 benign nodules, by fine-needle aspiration biopsy and surgery in 44 malignant and 15 benign lesions, and by surgery alone in five malignant and eight benign lesions. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated on the basis of our proposed classification method.Of 82 lesions classified as positive, 46 were malignant. Of 73 lesions classified as negative, three were malignant. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy based on our sonographic classification method were 93.8%, 66%, 56.1%, 95.9%, and 74.8%, respectively.Considering the high level of sensitivity of our proposed sonographic classification, fine-needle aspiration biopsy should be performed on thyroid nodules classified as positive, regardless of palpability.

BRAF Mutations in Thyroid Tumors Are Restricted to Papillary Carcinomas and Anaplastic or Poorly Differentiated Carcinomas Arising from Papillary Carcinomas

2003-11-01

Marina N. Nikiforova , Edna Teruko Kimura , Manoj Gandhi +7 more

Abstract Activating point mutations of the BRAF gene have been recently reported in papillary thyroid carcinomas. In this study, we analyzed 320 thyroid tumors and six anaplastic carcinoma cell lines … Abstract Activating point mutations of the BRAF gene have been recently reported in papillary thyroid carcinomas. In this study, we analyzed 320 thyroid tumors and six anaplastic carcinoma cell lines and detected BRAF mutations in 45 (38%) papillary carcinomas, two (13%) poorly-differentiated carcinomas, three (10%) anaplastic carcinomas, and five (83%) thyroid anaplastic carcinoma cell lines but not in follicular, Hürthle cell, and medullary carcinomas, follicular and Hürthle cell adenomas, or benign hyperplastic nodules. All mutations involved a T→A transversion at nucleotide 1796. In papillary carcinomas, BRAF mutations were associated with older age, classic papillary carcinoma or tall cell variant histology, extrathyroidal extension, and more frequent presentation at stages III and IV. All BRAF-positive poorly differentiated and anaplastic carcinomas contained areas of preexisting papillary carcinoma, and mutation was present in both the well-differentiated and dedifferentiated components. These data indicate that BRAF mutations are restricted to papillary carcinomas and poorly differentiated and anaplastic carcinomas arising from papillary carcinomas. They are associated with distinct phenotypical and biological properties of papillary carcinomas and may participate in progression to poorly differentiated and anaplastic carcinomas.

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Current Thyroid Cancer Trends in the United States

2014-03-10

Louise Davies , H. Gilbert Welch

We have previously reported on a doubling of thyroid cancer incidence-largely due to the detection of small papillary cancers. Because they are commonly found in people who have died of … We have previously reported on a doubling of thyroid cancer incidence-largely due to the detection of small papillary cancers. Because they are commonly found in people who have died of other causes, and because thyroid cancer mortality had been stable, we argued that the increased incidence represented overdiagnosis.To determine whether thyroid cancer incidence has stabilized.Analysis of secular trends in patients diagnosed with thyroid cancer, 1975 to 2009, using the Surveillance, Epidemiology, and End Results (SEER) program and thyroid cancer mortality from the National Vital Statistics System.Nine SEER areas (SEER 9): Atlanta, Georgia; Connecticut; Detroit, Michigan; Hawaii; Iowa; New Mexico; San Francisco-Oakland, California; Seattle-Puget Sound, Washington; and Utah.Men and women older than 18 years diagnosed as having a thyroid cancer between 1975 and 2009 who lived in the SEER 9 areas.None.Thyroid cancer incidence, histologic type, tumor size, and patient mortality. RESULTS Since 1975, the incidence of thyroid cancer has now nearly tripled, from 4.9 to 14.3 per 100,000 individuals (absolute increase, 9.4 per 100,000; relative rate [RR], 2.9; 95% CI, 2.7-3.1). Virtually the entire increase was attributable to papillary thyroid cancer: from 3.4 to 12.5 per 100,000 (absolute increase, 9.1 per 100,000; RR, 3.7; 95% CI, 3.4-4.0). The absolute increase in thyroid cancer in women (from 6.5 to 21.4 = 14.9 per 100,000 women) was almost 4 times greater than that of men (from 3.1 to 6.9 = 3.8 per 100,000 men). The mortality rate from thyroid cancer was stable between 1975 and 2009 (approximately 0.5 deaths per 100,000).There is an ongoing epidemic of thyroid cancer in the United States. The epidemiology of the increased incidence, however, suggests that it is not an epidemic of disease but rather an epidemic of diagnosis. The problem is particularly acute for women, who have lower autopsy prevalence of thyroid cancer than men but higher cancer detection rates by a 3:1 ratio.

Benign and Malignant Thyroid Nodules: US Differentiation—Multicenter Retrospective Study

2008-04-11

Won‐Jin Moon , So Lyung Jung , Jeong Hyun Lee +7 more

Purpose: To retrospectively evaluate the diagnostic accuracy of ultrasonographic (US) criteria for the depiction of benign and malignant thyroid nodules by using tissue diagnosis as the reference standard. Materials and … Purpose: To retrospectively evaluate the diagnostic accuracy of ultrasonographic (US) criteria for the depiction of benign and malignant thyroid nodules by using tissue diagnosis as the reference standard. Materials and Methods: This study had institutional review board approval, and informed consent was waived. From January 2003 through June 2003, 8024 consecutive patients had undergone thyroid US at nine affiliated hospitals. A total of 831 patients (716 women, 115 men; mean age, 49.5 years ± 13.8 [standard deviation]) with 849 nodules (360 malignant, 489 benign) that were diagnosed at surgery or biopsy were included in this study. Three radiologists retrospectively evaluated the following characteristics on US images: nodule size, presence of spongiform appearance, shape, margin, echotexture, echogenicity, and presence of microcalcification, macrocalcification, or rim calcification. A χ2 test and multiple regression analysis were performed. Sensitivity, specificity, and positive and negative predictive values were obtained. Results: Statistically significant (P < .05) findings of malignancy were a taller-than-wide shape (sensitivity, 40.0%; specificity, 91.4%), a spiculated margin (sensitivity, 48.3%; specificity, 91.8%), marked hypoechogenicity (sensitivity, 41.4%; specificity, 92.2%), microcalcification (sensitivity, 44.2%; specificity, 90.8%), and macrocalcification (sensitivity, 9.7%; specificity, 96.1%). The US findings for benign nodules were isoechogenicity (sensitivity, 56.6%; specificity, 88.1%; P < .001) and a spongiform appearance (sensitivity, 10.4%; specificity, 99.7%; P < .001). The presence of at least one malignant US finding had a sensitivity of 83.3%, a specificity of 74.0%, and a diagnostic accuracy of 78.0%. For thyroid nodules with a diameter of 1 cm or less, the sensitivity of microcalcifications was lower than that in larger nodules (36.6% vs 51.4%, P < .05). Conclusion: Shape, margin, echogenicity, and presence of calcification are helpful criteria for the discrimination of malignant from benign nodules; the diagnostic accuracy of US criteria is dependent on tumor size. © RSNA, 2008

Risk of Malignancy in Nonpalpable Thyroid Nodules: Predictive Value of Ultrasound and Color-Doppler Features

2002-05-01

Enrico Papini , Rinaldo Guglielmi , A. Bianchini +7 more

The aim of the study was to correlate the sonographic [ultrasound (US)] and color-Doppler (CFD) findings with the results of US-guided fine needle aspiration biopsy (FNA) and of pathologic staging … The aim of the study was to correlate the sonographic [ultrasound (US)] and color-Doppler (CFD) findings with the results of US-guided fine needle aspiration biopsy (FNA) and of pathologic staging of resected carcinomas to establish: 1) the relative importance of US features as risk factors of malignancy; and 2) a cost-effective management of nonpalpable thyroid nodules. Four hundred ninety-four consecutive patients with nonpalpable thyroid nodules (8–15 mm) were evaluated by US, CFD, and US-FNA. Ninety-two patients with inadequate cytology were excluded from the study. All patients with suspicious or malignant cytology underwent surgery, whereas subjects with benign cytology had clinical and US control 6 months later. Thyroid malignancies were observed in 18 of 195 (9.2%) solitary thyroid nodules and in 13 of 207 (6.3%) multinodular goiters. Cancer prevalence was similar in nodules greater or smaller than 10 mm (9.1 vs. 7.0%). Extracapsular growth (pT4) was present in 35.5%, and nodal involvement in 19.4% of neoplastic lesions, with no significant differences between tumors greater or smaller than 10 mm. At US cancers presented a solid hypoechoic appearance in 87% of cases, irregular or blurred margins in 77.4%, an intranodular vascular pattern in 74.2%, and microcalcifications in 29.0%. Irregular margins (RR 16.83), intranodular vascular spots (RR 14.29), and microcalcifications (RR 4.97) were independent risk factors of malignancy. FNA performed on hypoechoic nodules with at least one risk factor was able to identify 87% of the cancers at the expence of cytological evaluation of 38.4% of nonpalpable lesions. The majority of nonpalpable thyroid tumors can be identified by cytological evaluation of lesions presenting hypoechoic appearance in conjunction with one independent risk factor. Due to the nonnegligible prevalence of extracapsular growth and nodal metastasis, US-FNA should be performed on all 8–15 mm hypoechoic nodules with irregular margins, intranodular vascular spots or microcalcifications. Nonpalpable lesions of the thyroid without risk factors should be followed by means of clinical and US evaluation.

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Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer

2009-10-27

David S. Cooper , Gerard M. Doherty , Bryan R. Haugen +7 more

Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's guidelines for the management of these disorders … Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's guidelines for the management of these disorders was published in 2006, a large amount of new information has become available, prompting a revision of the guidelines.Relevant articles through December 2008 were reviewed by the task force and categorized by topic and level of evidence according to a modified schema used by the United States Preventative Services Task Force.The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to optimal surgical management, radioiodine remnant ablation, and suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using ultrasound and serum thyroglobulin as well as those related to management of recurrent and metastatic disease.We created evidence-based recommendations in response to our appointment as an independent task force by the American Thyroid Association to assist in the clinical management of patients with thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders.

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Management of Thyroid Nodules Detected at US: Society of Radiologists in Ultrasound Consensus Conference Statement

2005-12-01

Mary C. Frates , Carol B. Benson , J. William Charboneau +7 more

The Society of Radiologists in Ultrasound convened a panel of specialists from a variety of medical disciplines to come to a consensus on the management of thyroid nodules identified with … The Society of Radiologists in Ultrasound convened a panel of specialists from a variety of medical disciplines to come to a consensus on the management of thyroid nodules identified with thyroid ultrasonography (US), with particular focus on which nodules should be subjected to US-guided fine needle aspiration and which thyroid nodules need not be subjected to fine-needle aspiration. The panel met in Washington, DC, October 26–27, 2004, and created this consensus statement. The recommendations in this consensus statement, which are based on analysis of the current literature and common practice strategies, are thought to represent a reasonable approach to thyroid nodular disease. © RSNA, 2005

BRAF mutation in thyroid cancer

2005-06-01

Mingzhao Xing

Genetic alteration is the driving force for thyroid tumorigenesis and progression, based upon which novel approaches to the management of thyroid cancer can be developed. A recent important genetic finding … Genetic alteration is the driving force for thyroid tumorigenesis and progression, based upon which novel approaches to the management of thyroid cancer can be developed. A recent important genetic finding in thyroid cancer is the oncogenic T1799A transversion mutation of BRAF (the gene for the B-type Raf kinase, BRAF). Since the initial report of this mutation in thyroid cancer 2 years ago, rapid advancements have been made. BRAF mutation is the most common genetic alteration in thyroid cancer, occurring in about 45% of sporadic papillary thyroid cancers (PTCs), particularly in the relatively aggressive subtypes, such as the tall-cell PTC. This mutation is mutually exclusive with other common genetic alterations, supporting its independent oncogenic role, as demonstrated by transgenic mouse studies that showed BRAF mutation-initiated development of PTC and its transition to anaplastic thyroid cancer. BRAF mutation is mutually exclusive with RET/PTC rearrangement, and also displays a reciprocal age association with this common genetic alteration in thyroid cancer. The T1799A BRAF mutation occurs exclusively in PTC and PTC-derived anaplastic thyroid cancer and is a specific diagnostic marker for this cancer when identified in cytological and histological specimens. This mutation is associated with a poorer clinicopathological outcome and is a novel independent molecular prognostic marker in the risk evaluation of thyroid cancer. Moreover, preclinical and clinical evaluations of the therapeutic value of novel specific mitogen-activated protein kinase pathway inhibitors in thyroid cancer are anticipated. This newly discovered BRAF mutation may prove to have an important impact on thyroid cancer in the clinic.

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Vandetanib in Patients With Locally Advanced or Metastatic Medullary Thyroid Cancer: A Randomized, Double-Blind Phase III Trial

2011-10-25

Samuel A. Wells , Bruce G. Robinson , Robert F. Gagel +7 more

There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor … There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, has previously shown antitumor activity in a phase II study of patients with advanced hereditary MTC.Patients with advanced MTC were randomly assigned in a 2:1 ratio to receive vandetanib 300 mg/d or placebo. On objective disease progression, patients could elect to receive open-label vandetanib. The primary end point was progression-free survival (PFS), determined by independent central Response Evaluation Criteria in Solid Tumors (RECIST) assessments.Between December 2006 and November 2007, 331 patients (mean age, 52 years; 90% sporadic; 95% metastatic) were randomly assigned to receive vandetanib (231) or placebo (100). At data cutoff (July 2009; median follow-up, 24 months), 37% of patients had progressed and 15% had died. The study met its primary objective of PFS prolongation with vandetanib versus placebo (hazard ratio [HR], 0.46; 95% CI, 0.31 to 0.69; P < .001). Statistically significant advantages for vandetanib were also seen for objective response rate (P < .001), disease control rate (P = .001), and biochemical response (P < .001). Overall survival data were immature at data cutoff (HR, 0.89; 95% CI, 0.48 to 1.65). A final survival analysis will take place when 50% of the patients have died. Common adverse events (any grade) occurred more frequently with vandetanib compared with placebo, including diarrhea (56% v 26%), rash (45% v 11%), nausea (33% v 16%), hypertension (32% v 5%), and headache (26% v 9%).Vandetanib demonstrated therapeutic efficacy in a phase III trial of patients with advanced MTC (ClinicalTrials.gov NCT00410761).

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Cabozantinib in Progressive Medullary Thyroid Cancer

2013-09-04

Rossella Elisei , Martin Schlumberger , Stefan Müller +7 more

Cabozantinib, a tyrosine kinase inhibitor (TKI) of hepatocyte growth factor receptor (MET), vascular endothelial growth factor receptor 2, and rearranged during transfection (RET), demonstrated clinical activity in patients with medullary … Cabozantinib, a tyrosine kinase inhibitor (TKI) of hepatocyte growth factor receptor (MET), vascular endothelial growth factor receptor 2, and rearranged during transfection (RET), demonstrated clinical activity in patients with medullary thyroid cancer (MTC) in phase I.We conducted a double-blind, phase III trial comparing cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomly assigned (2:1) to cabozantinib (140 mg per day) or placebo. The primary end point was progression-free survival (PFS). Additional outcome measures included tumor response rate, overall survival, and safety.The estimated median PFS was 11.2 months for cabozantinib versus 4.0 months for placebo (hazard ratio, 0.28; 95% CI, 0.19 to 0.40; P < .001). Prolonged PFS with cabozantinib was observed across all subgroups including by age, prior TKI treatment, and RET mutation status (hereditary or sporadic). Response rate was 28% for cabozantinib and 0% for placebo; responses were seen regardless of RET mutation status. Kaplan-Meier estimates of patients alive and progression-free at 1 year are 47.3% for cabozantinib and 7.2% for placebo. Common cabozantinib-associated adverse events included diarrhea, palmar-plantar erythrodysesthesia, decreased weight and appetite, nausea, and fatigue and resulted in dose reductions in 79% and holds in 65% of patients. Adverse events led to treatment discontinuation in 16% of cabozantinib-treated patients and in 8% of placebo-treated patients.Cabozantinib (140 mg per day) achieved a statistically significant improvement of PFS in patients with progressive metastatic MTC and represents an important new treatment option for patients with this rare disease. This dose of cabozantinib was associated with significant but manageable toxicity.

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Thyroid Imaging Reporting and Data System for US Features of Nodules: A Step in Establishing Better Stratification of Cancer Risk

2011-07-20

Jin Young Kwak , Kyunghwa Han , Jung Hyun Yoon +7 more

Purpose To develop a practical thyroid imaging reporting and data system (TIRADS) with which to categorize thyroid nodules and stratify their malignant risk. Materials and Methods The institutional review board … Purpose To develop a practical thyroid imaging reporting and data system (TIRADS) with which to categorize thyroid nodules and stratify their malignant risk. Materials and Methods The institutional review board approved this retrospective study, and the requirement to obtain informed consent for the review of images and records was waived. From May to December 2008, ultrasonographically (US)-guided fine-needle aspiration biopsy (FNAB) was performed in 3674 focal thyroid nodules in 3414 consecutive patients. The study included the 1658 thyroid nodules (≥1 cm in maximum diameter at US) in 1638 patients (1373 women, 265 men) for which pathologic diagnosis or follow-up findings were available. Univariate and multivariate analyses with generalized estimating equations were performed to investigate the relationship between suspicious US features and thyroid cancer. A score for each significant factor was assigned and multiplied by the β coefficient obtained for each significant factor from multivariate logistic regression analysis. Scores for each significant factor were then added, resulting in an equation that fitted the probability of malignancy in thyroid nodules. The authors evaluated the fitted probability by using a regression equation; the risk of malignancy was determined according to the number of suspicious US features. Results The following US features showed a significant association with malignancy: solid component, hypoechogenicity, marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, and taller-than-wide shape. As the number of suspicious US features increased, the fitted probability and risk of malignancy also increased. Positive predictive values according to the number of suspicious US features were significantly different (P < .001). Conclusion Risk stratification of thyroid malignancy by using the number of suspicious US features allows for a practical and convenient TIRADS. © RSNA, 2011

2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer

2015-10-14

Bryan R. Haugen , Erik K. Alexander , Keith C. Bible +7 more

Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were … Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations for therapeutic interventions. We developed a similarly formatted system to appraise the quality of such studies and resultant recommendations. The guideline panel had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, use of molecular markers, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to screening for thyroid cancer, staging and risk assessment, surgical management, radioiodine remnant ablation and therapy, and thyrotropin suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using imaging and serum thyroglobulin, thyroid hormone therapy, management of recurrent and metastatic disease, consideration for clinical trials and targeted therapy, as well as directions for future research. Conclusions: We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders.

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Preoperative Diagnosis of Benign Thyroid Nodules with Indeterminate Cytology

2012-06-25

Erik K. Alexander , Giulia C. Kennedy , Zubair Baloch +7 more

Approximately 15 to 30% of thyroid nodules evaluated by means of fine-needle aspiration are not clearly benign or malignant. Patients with cytologically indeterminate nodules are often referred for diagnostic surgery, … Approximately 15 to 30% of thyroid nodules evaluated by means of fine-needle aspiration are not clearly benign or malignant. Patients with cytologically indeterminate nodules are often referred for diagnostic surgery, though most of these nodules prove to be benign. A novel diagnostic test that measures the expression of 167 genes has shown promise in improving preoperative risk assessment.We performed a 19-month, prospective, multicenter validation study involving 49 clinical sites, 3789 patients, and 4812 fine-needle aspirates from thyroid nodules 1 cm or larger that required evaluation. We obtained 577 cytologically indeterminate aspirates, 413 of which had corresponding histopathological specimens from excised lesions. Results of a central, blinded histopathological review served as the reference standard. After inclusion criteria were met, a gene-expression classifier was used to test 265 indeterminate nodules in this analysis, and its performance was assessed.Of the 265 indeterminate nodules, 85 were malignant. The gene-expression classifier correctly identified 78 of the 85 nodules as suspicious (92% sensitivity; 95% confidence interval [CI], 84 to 97), with a specificity of 52% (95% CI, 44 to 59). The negative predictive values for "atypia (or follicular lesion) of undetermined clinical significance," "follicular neoplasm or lesion suspicious for follicular neoplasm," or "suspicious cytologic findings" were 95%, 94%, and 85%, respectively. Analysis of 7 aspirates with false negative results revealed that 6 had a paucity of thyroid follicular cells, suggesting insufficient sampling of the nodule.These data suggest consideration of a more conservative approach for most patients with thyroid nodules that are cytologically indeterminate on fine-needle aspiration and benign according to gene-expression classifier results. (Funded by Veracyte.).

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European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium

2006-05-25

Furio Pacini , Martin Schlumberger , Henning Dralle +4 more

Journal Article European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium Get access Furio Pacini, Furio Pacini Section of Endocrinology and Metabolism, University of … Journal Article European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium Get access Furio Pacini, Furio Pacini Section of Endocrinology and Metabolism, University of Siena, Via Bracci, 53100 Siena, Italy (Correspondence should be addressed to F Pacini; Email: [email protected]) Search for other works by this author on: Oxford Academic Google Scholar Martin Schlumberger, Martin Schlumberger Service de Médicine Nucléaire, Institut Gustave Roussy, Villejuif, France Search for other works by this author on: Oxford Academic Google Scholar Henning Dralle, Henning Dralle Department of General, Visceral and Vascular Surgery, University of Halle, Germany Search for other works by this author on: Oxford Academic Google Scholar Rossella Elisei, Rossella Elisei Department of Endocrinology, University of Pisa, Italy Search for other works by this author on: Oxford Academic Google Scholar Johannes W A Smit, Johannes W A Smit Department of Endocrinology and Metabolic Disease, Leiden University Medical Center, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar Wilmar Wiersinga, Wilmar Wiersinga Department of Endocrinology and Metabolism, University of Amsterdam, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar the European Thyroid Cancer Taskforce the European Thyroid Cancer Taskforce Search for other works by this author on: Oxford Academic Google Scholar European Journal of Endocrinology, Volume 154, Issue 6, Jun 2006, Pages 787–803, https://doi.org/10.1530/eje.1.02158 Published: 01 June 2006 Article history Received: 10 February 2006 Accepted: 03 March 2006 Published: 01 June 2006

Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial

2014-04-24

Marcia S. Brose , Christopher M. Nutting , Barbara Jarząb +7 more

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Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers

2016-02-14

Iñigo Landa , Tihana Ibrahimpašić , Laura Boucai +7 more

BACKGROUND. Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) are rare and frequently lethal tumors that so far have not been subjected to comprehensive genetic characterization. BACKGROUND. Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) are rare and frequently lethal tumors that so far have not been subjected to comprehensive genetic characterization.

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Korea's Thyroid-Cancer “Epidemic” — Screening and Overdiagnosis

2014-11-05

Hyeong Sik Ahn , Hyun Jung Kim , H. Gilbert Welch

In 2011, the rate of thyroid-cancer diagnoses in the Republic of Korea was 15 times that observed in 1993, yet thyroid-cancer mortality remains stable — a combination that suggests that … In 2011, the rate of thyroid-cancer diagnoses in the Republic of Korea was 15 times that observed in 1993, yet thyroid-cancer mortality remains stable — a combination that suggests that the problem is overdiagnosis attributable to widespread thyroid-cancer screening.

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer

2015-04-22

Gary L. Francis , Steven G. Waguespack , Andrew J. Bauer +7 more

Background: Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in … Background: Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed. Methods: A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force. Results: These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided. Conclusions: In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the management of thyroid nodules and DTC in children and adolescents. In our opinion, these represent the current optimal care for children and adolescents with these conditions.

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Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma

2016-04-14

Yuri E. Nikiforov , Raja R. Seethala , Giovanni Tallini +7 more

Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer.To evaluate clinical … Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer.To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC.International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature.Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria.Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10-26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3% (95% CI, 92.1%-96.0%) for NIFTP.Thyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.

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American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules - 2016 Update Appendix

2016-05-01

Hossein Gharib , Enrico Papini , Jeffrey R. Garber +6 more

Trends in Thyroid Cancer Incidence and Mortality in the United States, 1974-2013

2017-03-31

Hyeyeun Lim , Susan S. Devesa , Julie Ann Sosa +2 more

Thyroid cancer incidence has increased substantially in the United States over the last 4 decades, driven largely by increases in papillary thyroid cancer. It is unclear whether the increasing incidence … Thyroid cancer incidence has increased substantially in the United States over the last 4 decades, driven largely by increases in papillary thyroid cancer. It is unclear whether the increasing incidence of papillary thyroid cancer has been related to thyroid cancer mortality trends.To compare trends in thyroid cancer incidence and mortality by tumor characteristics at diagnosis.Trends in thyroid cancer incidence and incidence-based mortality rates were evaluated using data from the Surveillance, Epidemiology, and End Results-9 (SEER-9) cancer registry program, and annual percent change in rates was calculated using log-linear regression.Tumor characteristics.Annual percent changes in age-adjusted thyroid cancer incidence and incidence-based mortality rates by histologic type and SEER stage for cases diagnosed during 1974-2013.Among 77 276 patients (mean [SD] age at diagnosis, 48 [16] years; 58 213 [75%] women) diagnosed with thyroid cancer from 1974-2013, papillary thyroid cancer was the most common histologic type (64 625 cases), and 2371 deaths from thyroid cancer occurred during 1994-2013. Thyroid cancer incidence increased, on average, 3.6% per year (95% CI, 3.2%-3.9%) during 1974-2013 (from 4.56 per 100 000 person-years in 1974-1977 to 14.42 per 100 000 person-years in 2010-2013), primarily related to increases in papillary thyroid cancer (annual percent change, 4.4% [95% CI, 4.0%-4.7%]). Papillary thyroid cancer incidence increased for all SEER stages at diagnosis (4.6% per year for localized, 4.3% per year for regional, 2.4% per year for distant, 1.8% per year for unknown). During 1994-2013, incidence-based mortality increased 1.1% per year (95% CI, 0.6%-1.6%) (from 0.40 per 100 000 person-years in 1994-1997 to 0.46 per 100 000 person-years in 2010-2013) overall and 2.9% per year (95% CI, 1.1%-4.7%) for SEER distant stage papillary thyroid cancer.Among patients in the United States diagnosed with thyroid cancer from 1974-2013, the overall incidence of thyroid cancer increased 3% annually, with increases in the incidence rate and thyroid cancer mortality rate for advanced-stage papillary thyroid cancer. These findings are consistent with a true increase in the occurrence of thyroid cancer in the United States.

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ACR Thyroid Imaging, Reporting and Data System (TI-RADS): White Paper of the ACR TI-RADS Committee

2017-04-02

Franklin N. Tessler , William D. Middleton , Edward G. Grant +7 more

Papillary and Follicular Thyroid Carcinoma

1998-01-29

Martin Schlumberger

Papillary and follicular (differentiated) thyroid carcinomas are among the most curable cancers. However, some patients are at high risk for recurrent disease or even death. Most of these patients can … Papillary and follicular (differentiated) thyroid carcinomas are among the most curable cancers. However, some patients are at high risk for recurrent disease or even death. Most of these patients can be identified at the time of diagnosis by using well-established prognostic indicators. The extent of the initial treatment and follow-up care should therefore be tailored to the level of risk. Although treatment guidelines have been published,1,2 clinical procedures vary considerably among clinicians.3 EpidemiologyAlthough thyroid nodules are common, differentiated thyroid carcinomas are relatively rare. Clinically detectable thyroid carcinomas constitute less than 1 percent of all human cancers. The annual . . .

European Thyroid Association Guidelines for Ultrasound Malignancy Risk Stratification of Thyroid Nodules in Adults: The EU-TIRADS

2017-01-01

Gilles Russ , Steen Joop Bonnema , Murat Faik Erdoğan +3 more

Thyroid ultrasound (US) is a key examination for the management of thyroid nodules. Thyroid US is easily accessible, noninvasive, and cost-effective, and is a mandatory step in the workup of … Thyroid ultrasound (US) is a key examination for the management of thyroid nodules. Thyroid US is easily accessible, noninvasive, and cost-effective, and is a mandatory step in the workup of thyroid nodules. The main disadvantage of the method is that it is operator dependent. Thyroid US assessment of the risk of malignancy is crucial in patients with nodules, in order to select those who should have a fine needle aspiration (FNA) biopsy performed. Due to the pivotal role of thyroid US in the management of patients with nodules, the European Thyroid Association convened a panel of international experts to set up European guidelines on US risk stratification of thyroid nodules. Based on a review of the literature and on the American Association of Clinical Endocrinologists, American Thyroid Association, and Korean guidelines, the panel created the novel European Thyroid Imaging and Reporting Data System, called EU-TIRADS. This comprises a thyroid US lexicon; a standardized report; definitions of benign and low-, intermediate-, and high-risk nodules, with the estimated risks of malignancy in each category; and indications for FNA. Illustrated by numerous US images, the EU-TIRADS aims to serve physicians in their clinical practice, to enhance the interobserver reproducibility of descriptions, and to simplify communication of the results.

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The 2017 Bethesda System for Reporting Thyroid Cytopathology

2017-11-01

Edmund S. Cibas , Syed Z. Ali

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) established a standardized, category-based reporting system for thyroid fine-needle aspiration (FNA) specimens. The 2017 revision reaffirms that every thyroid FNA report should … The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) established a standardized, category-based reporting system for thyroid fine-needle aspiration (FNA) specimens. The 2017 revision reaffirms that every thyroid FNA report should begin with one of six diagnostic categories, the names of which remain unchanged since they were first introduced: (i) nondiagnostic or unsatisfactory; (ii) benign; (iii) atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS); (iv) follicular neoplasm or suspicious for a follicular neoplasm; (v) suspicious for malignancy; and (vi) malignant. There is a choice of two different names for some of the categories. A laboratory should choose the one it prefers and use it exclusively for that category. Synonymous terms (e.g., AUS and FLUS) should not be used to denote two distinct interpretations. Each category has an implied cancer risk that ranges from 0% to 3% for the "benign" category to virtually 100% for the "malignant" category, and, in the 2017 revision, the malignancy risks have been updated based on new (post 2010) data. As a function of their risk associations, each category is linked to updated, evidence-based clinical management recommendations. The recent reclassification of some thyroid neoplasms as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has implications for the risk of malignancy, and this is accounted for with regard to diagnostic criteria and optional notes. Such notes can be useful in helping guide surgical management.

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The Bethesda System for Reporting Thyroid Cytopathology

2009-11-01

Edmund S. Cibas , Syed Z. Ali

Objective: To address terminology and other issues related to thyroid fine-needle aspiration (FNA), the National Cancer Institute (NCI) hosted The NCI Thyroid FNA State of the Science Conference. The conclusions … Objective: To address terminology and other issues related to thyroid fine-needle aspiration (FNA), the National Cancer Institute (NCI) hosted The NCI Thyroid FNA State of the Science Conference. The conclusions regarding terminology and morphologic criteria from the NCI meeting led to the Bethesda Thyroid Atlas Project and form the framework for the Bethesda System for Reporting Thyroid Cytopathology. Design: Participants of the Atlas Project were selected from among the committee members of the NCI FNA State of the Science Conference and other participants at the live conference. The terminology framework was based on a literature search of English language publications dating back to 1995 using PubMed as the search engine; online forum discussions (http://thyroidfna.cancer.gov/forums/default.aspx); and formal interdisciplinary discussions held on October 22 and 23, 2007, in Bethesda, MD. Main Outcome: For clarity of communication, the Bethesda System for Reporting Thyroid Cytopathology recommends that each report begin with one of the six general diagnostic categories. Each of the categories has an implied cancer risk that links it to an appropriate clinical management guideline. Conclusions: The project participants hope that the adoption of this framework will facilitate communication among cytopathologists, endocrinologists, surgeons, and radiologists; facilitate cytologic–histologic correlation for thyroid diseases; facilitate research into the understanding of thyroid diseases; and allow easy and reliable sharing of data from different laboratories for national and international collaborative studies.

Thyroid cancer

2016-05-29

Maria E. Cabanillas , David G. McFadden , Cosimo Durante

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Thyroid Cancer after Exposure to External Radiation: A Pooled Analysis of Seven Studies

1995-03-01

Elaine Ron , Jay H. Lubin , Roy E. Shore +6 more

Comparison of total thyroidectomy and lobectomy for intermediate-risk papillary thyroid carcinoma with lateral lymph node metastasis: a systematic review and meta-analysis

2025-06-25

Xinhua Li , Zhiqiang Gui , C. F. Xu +6 more | International Journal of Surgery

Distinctive hobnail subtype of papillary thyroid carcinoma: a case series and short review of literature

2025-06-25

Vishal Yadav , Anupam Lahiri , Sunil Pasricha +4 more | HORMONES

Pure red-cell aplasia after radioactive iodine treatment in a patient with papillary thyroid cancer and follow up for two years: a case report

2025-06-24

Rui Li , Meng Wang , Shaoxin Li +1 more | Frontiers in Oncology

Acquired pure red cell aplasia (PRCA) has attracted more and more attention in hematology. PRCA usually caused by infection, autoimmune diseases, thymic carcinoma, or drugs, has not been reported by … Acquired pure red cell aplasia (PRCA) has attracted more and more attention in hematology. PRCA usually caused by infection, autoimmune diseases, thymic carcinoma, or drugs, has not been reported by radioactive iodine. Here we report a case of PRCA after radioactive iodine therapies (two times, 100 mCi and 130 mCi each) in a patient with papillary thyroid carcinoma and follow up for two years. she was treatment with cyclosporine (100mg twice per day), stanozolol (2mg three times per day) and diammonium glycyrrhizinate (150mg three times per day), returned to the normal range in 2024.

Dynamic risk stratification-guided management of medullary thyroid carcinoma: integrating surgical precision with RET-targeted therapies and molecular surveillance

2025-06-24

Jiao Zhang , Gianlorenzo Dionigi , Hoon Yub Kim +2 more | International Journal of Surgery

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine neoplasm derived from parafollicular C cells of the thyroid gland, primarily driven by alterations in the RET oncogene. This review focuses on … Medullary thyroid carcinoma (MTC) is a rare neuroendocrine neoplasm derived from parafollicular C cells of the thyroid gland, primarily driven by alterations in the RET oncogene. This review focuses on the current advances in treatment modalities for MTCs, encompassing surgical interventions, targeted therapy, postoperative surveillance, and future challenges. Total thyroidectomy is the primary curative approach for MTCs. However, the extent of lymph node dissection, particularly lateral neck dissection, remains controversial. Postoperative surveillance involves monitoring serum calcitonin and carcinoembryonic antigen levels, imaging assessments, and dynamic risk stratification to detect recurrence. Drug therapy offers an alternative approach in cases of challenging surgical scenarios or advanced MTCs. Multi-kinase inhibitors (e.g. vandetanib and cabozantinib) have shown increased survival outcomes for metastatic MTCs and are approved as effective treatment options. More recently, selective RET inhibitors like selpercatinib and pralsetinib have demonstrated higher efficacy and better tolerability. Despite these advances, challenges persist in managing MTCs, including addressing biochemical recurrence, determining surgical scope, considering immunotherapy, and treating advanced cases. Personalized medicine approaches, incorporating genetic screening, and innovative therapies, are essential for improving survival and quality of life in MTC patients.

Diagnostic performance of contrast‑enhanced ultrasound vs. conventional ultrasound for lymph node metastasis in patients with thyroid cancer: A meta‑analysis

2025-06-24

Junhui Gao , Ying Liu , Lipeng Zheng +3 more | Oncology Letters

The ability of conventional ultrasound (US) and contrast-enhanced (CE)US to diagnose lymph node metastasis in patients with thyroid cancer has been explored, but there is a lack of a pooled … The ability of conventional ultrasound (US) and contrast-enhanced (CE)US to diagnose lymph node metastasis in patients with thyroid cancer has been explored, but there is a lack of a pooled analysis. In the present study, a meta-analysis was performed to explore the diagnostic performance of conventional US and CEUS for lymph node metastasis in patients with thyroid cancer. The PubMed, Web of Science, Embase and Cochrane Library databases were searched to identify studies related to the diagnosis of lymph node metastasis using CEUS and conventional US in patients with thyroid cancer published until February 2024. This meta-analysis incorporated 9 studies, involving a total of 1,226 patients with thyroid cancer. The quality assessment of diagnostic accuracy studies-2 tool suggested that the quality of the included studies was good. A summary receiver operating characteristic analysis was performed to assess the diagnostic performance of conventional US and CEUS. The pooled sensitivity [95% confidence interval (CI)], specificity (95% CI) and the area under curve (AUC) of conventional US for diagnosing lymph node metastasis were 0.77 (0.73-0.80), 0.72 (0.68-0.76) and 0.7925, respectively, in patients with thyroid cancer, while the parameters of CEUS were 0.85 (0.82-0.88), 0.86 (0.82-0.89) and 0.9216, respectively. Overall, the pooled sensitivity, specificity and AUC of CEUS for diagnosing lymph node metastasis were higher than those of conventional US in patients with thyroid cancer (all P<0.001). Deeks' asymmetry test suggested that no publication bias existed in this meta-analysis. In conclusion, CEUS shows a better ability to diagnose lymph node metastasis than the conventional US in patients with thyroid cancer.

A Rare Concurrence of Anaplastic and Papillary Thyroid Carcinomas: A Case Report and Literature Review

2025-06-23

Monika Maharjan , Zahed Ali Qamer , Bheru Dan Charan +2 more | Indian Journal of Otolaryngology and Head & Neck Surgery

Evaluation of Factors Associated with Recurrent Differentiated Thyroid Cancer in Patients Who Underwent Total Thyroidectomy and Radioiodine Therapy with Biochemical Incomplete Responses

2025-06-23

| Journal of the Medical Association of Thailand

Objective: The objectives of the present study were 1) to evaluate the factors that predict the recurrence of thyroid cancer in patients with biochemical incomplete responses (BIR) and differentiated thyroid … Objective: The objectives of the present study were 1) to evaluate the factors that predict the recurrence of thyroid cancer in patients with biochemical incomplete responses (BIR) and differentiated thyroid cancer (DTC) patients who were treated with total thyroidectomy and radioiodine-131, 2) to determine the distribution and location of recurrences, and 3) to assess the serial serum thyroglobulin (Tg) and thyroglobulin antibodies (TgAb) to determine the diagnostic accuracy for disease recurrence. Materials and Methods: The authors retrospectively reviewed 203 BIR patients treated between January 2004 and December 2014. Data were recorded on case report forms, including age at the time of first radioiodine-131 treatment, gender, diagnosis, surgical history, Tg and TgAb levels, pathological examination results, and radiology findings from radioiodine-131 whole-body scanning, computed tomography (CT), neck ultrasound, and F-18 FDG PET/CT scans. The 203 patients were classified into two groups, recurrence patients with 54 patients (26.6%), and non-recurrence patients with 149 patients (73.4%). Results: The number and percentage of local recurrences or metastatic lesions were cervical lymph node metastasis in 26 patients (48.1%), local recurrence in 18 patients (33.3%), lung metastasis in 11 patients (20.4%), and bone metastasis in one patient (1.9%). Two patients had lesions in both the surgical site and cervical lymph nodes. Statistically significant clinical characteristics between the two groups included age, the American Thyroid Association (ATA) 2015 risk of recurrence, and lymph node metastasis. Optimal thresholds for recurrence were identified as a Tg velocity greater than 0.6 ng/mL/year, a Tg doubling time of less than 3.5 years, and a TgAb velocity greater than 0 IU/mL/year. Conclusion: Risk factors for local recurrences or metastatic lesions in BIR patients include older age, lymph node metastasis, ATA high risk stratification, Tg velocity at 0.6 ng/mL/year or greater, Tg doubling time in less than 3.5 years, and TgAb velocity greater than 0 IU/mL/year. Close follow-up with CT neck and chest is recommended to detect cervical lymph node metastasis, local recurrences, and lung metastasis.

From lungs to thyroid: A rare metastatic journey of papillary adenocarcinoma of the lung

2025-06-23

Sonali Mallik , Swagatika Samal , Amanpreet Kaur +1 more | Annals of Thoracic Medicine

ABSTRACT The metastasis from a primary lung adenocarcinoma to the thyroid is an infrequent occurrence. Typically, malignancies arising from the breast or kidney are more commonly associated with metastatic involvement … ABSTRACT The metastasis from a primary lung adenocarcinoma to the thyroid is an infrequent occurrence. Typically, malignancies arising from the breast or kidney are more commonly associated with metastatic involvement of the thyroid gland. Here, we report the case of a 63-year-old female with primary lung papillary adenocarcinoma presenting moderate thyroid swelling and progressive shortness of breath. Ultrasound of the neck demonstrated diffusely enlarged and heterogeneously hypoechoic thyroid parenchyma, accompanied by microcalcifications and bilateral enlargement of level III and IV lymph nodes. Fine-needle aspiration cytology of the thyroid gland revealed papillary carcinoma, The Bethesda category VI. Immunocytochemistry positive for TTF1 and Napsin A and negative for PAX 8 proved it to be a primary lung papillary adenocarcinoma metastasizing to the thyroid. Contrast-enhanced computed tomography of the thorax demonstrated gross right pleural effusion with collapse and consolidation of the entire lung parenchyma. This case highlights the importance of cell block and immunocytochemistry in the accurate diagnosis of metastatic thyroid malignancy.

Inibitori multichinasici nel trattamento del carcinoma differenziato tiroideo iodio-refrattario

2025-06-23

Vincenzo Marotta | L Endocrinologo

When Diarrhea Tells a Deeper Story: A Curious Case of Metastatic Medullary Thyroid Carcinoma

2025-06-22

Milan Shrestha , Abhyuday Kumar Yadav , Ramila Shrestha +2 more | Cureus

Papillary thyroid carcinoma

2025-06-20

Henry Knipe | Radiopaedia.org

The management of cytologically indeterminate thyroid nodules in clinical practice: A contemporary perspective with focus on molecular imaging

2025-06-20

Petra Petranović Ovčariček , Alfredo Campennì , Massimo Bongiovanni +1 more | Endocrine

Exploring the Potential of ChatGPT-4o in Thyroid Nodule Diagnosis Using Multi-Modality Ultrasound Imaging: Dual- vs. Triple-Modality Approaches

2025-06-20

Ziman Chen , Nonhlanhla Chambara , Shirley Yuk‐Wah Liu +3 more | Cancers

Background/Objectives Recent advancements in large language models, such as ChatGPT-4o, have created new opportunities for analyzing complex multi-modal data, including medical images. This study aims to assess the potential of … Background/Objectives Recent advancements in large language models, such as ChatGPT-4o, have created new opportunities for analyzing complex multi-modal data, including medical images. This study aims to assess the potential of ChatGPT-4o in distinguishing between benign and malignant thyroid nodules via multi-modality ultrasound imaging: grayscale ultrasound, color Doppler ultrasound (CDUS), and shear wave elastography (SWE). Materials and Methods Patients who underwent thyroid nodule ultrasound examinations and had confirmed pathological diagnoses were included. ChatGPT-4o analyzed the multi-modality ultrasound data using two approaches: (1.) a dual-modality strategy which employed grayscale ultrasound and CDUS, and (2.) a triple-modality strategy which incorporated grayscale ultrasound, CDUS, and SWE. The diagnostic performance was compared against pathological findings utilizing receiver operating characteristic (ROC) curve analysis, while consistency was evaluated through Cohen’s Kappa analysis. Results A total of 106 thyroid nodules were evaluated; 65.1% were benign and 34.9% malignant. In the dual-modality approach, ChatGPT-4o achieved an area under the ROC curve (AUC) of 66.3%, moderate agreement with pathology results (Kappa = 0.298), a sensitivity of 70.3%, a specificity of 62.3%, and an accuracy of 65.1%. Conversely, the triple-modality approach exhibited higher specificity at 97.1% but lower sensitivity at 18.9%, with an accuracy of 69.8% and a reduced overall agreement (Kappa = 0.194), resulting in an AUC of 58.0%. Conclusions ChatGPT-4o exhibits potential, to some extent, in classifying thyroid nodules using multi-modality ultrasound imaging. However, the dual-modality approach unexpectedly outperforms the triple-modality approach. This indicates that ChatGPT-4o might encounter challenges in integrating and prioritizing different data modalities, particularly when conflicting information is present, which could impact diagnostic effectiveness.

Thyroid follicular adenoma

2025-06-19

Henry Knipe | Radiopaedia.org

Papillary thyroid carcinoma

2025-06-19

Henry Knipe | Radiopaedia.org

Papillary thyroid carcinoma

2025-06-19

Henry Knipe | Radiopaedia.org

Predictive analytics for thyroid cancer recurrence: a feature selection and data balancing approach

2025-06-19

İrem Şenyer Yapıcı , Rukiye Uzun Arslan | The European Physical Journal Special Topics

Abstract Thyroid cancer recurrence presents considerable challenges in clinical practice, underscoring the need for accurate predictive models to guide timely interventions. This study introduces a hybrid machine learning (ML) framework … Abstract Thyroid cancer recurrence presents considerable challenges in clinical practice, underscoring the need for accurate predictive models to guide timely interventions. This study introduces a hybrid machine learning (ML) framework that combines data balancing and feature selection to enhance recurrence prediction. Utilizing the Differentiated Thyroid Cancer Recurrence dataset, the framework evaluates the performance of nine distinct ML classifiers through an 80:20 stratified train-test split and stratified 5-fold cross-validation. Among the evaluated models, ensemble methods—particularly Random Forest and Bagging—demonstrate superior performance on SMOTE-balanced data, achieving $$98.7\%$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>98.7</mml:mn> <mml:mo>%</mml:mo> </mml:mrow> </mml:math> accuracy and $$95.5\%$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>95.5</mml:mn> <mml:mo>%</mml:mo> </mml:mrow> </mml:math> recall, and outperforming previously reported methods. Statistical analyses further confirm that the impact of feature selection techniques varies depending on classifier architecture. Overall, the proposed framework illustrates that combining data balancing with informed feature selection significantly enhances predictive performance and contributes to the development of reliable decision-support systems for the early detection of thyroid cancer recurrence. The framework’s interpretability and robustness underscore its potential for integration into clinical decision-support systems, enabling early recurrence detection and facilitating personalized treatment strategies. These findings are also applicable to other imbalanced medical datasets.

<b>DUAL-TRACER PET/CT IMAGING IN THYROID CARCINOMA: COMPLEMENTARY ROLES OF ¹⁸F-FDG AND ⁶⁸GA-DOTATATE IN DETECTING RECURRENCE AND METASTASIS</b>

2025-06-19

Kanwal Bano , Maaz Khan , Aliya Akhlaq +1 more | Journal of medical & health sciences review.

Background: Thyroid carcinoma is a highly aggressive tumor, often giving rise to recurrent cancer and metastatic cancer even after the surgical treatment. Early detection of thyroid cancer is essential for … Background: Thyroid carcinoma is a highly aggressive tumor, often giving rise to recurrent cancer and metastatic cancer even after the surgical treatment. Early detection of thyroid cancer is essential for improving long term treatment and patient survival rate. Objective: To compare the diagnostic accuracy of PET/ CT with the conventional methods and radioactive iodine scans in the management of thyroid cancer. Methodology: Published reports of comparing the diagnostic accuracy of PET/ CT with the conventional methods and radioactive iodine scans in the management of thyroid cancer were identified by a systematic search of Google Scholar, PubMed, Research Gate, Springer and the Sci Hub, supplemented with citation tracking. From 1001 initially identified studies, only 13 studies met the inclusion criteria after screening and duplicate removal. These studies compared the diagnostic accuracy of PET/ CT with the conventional methods and radioactive iodine scans in the management of thyroid cancer, using standard statistical measures, typically at a 95% confidence level. Results: The literature reviewed reveals that PET/CT imaging, especially when using 18F-FDG, is important in managing thyroid cancer especially when the conventional imaging tools such as radioactive iodine (RAI) scans and ultrasound fail to clearly indicate the condition. PET/CT has a good diagnostic accuracy in the diagnosis of recurrent or metastatic disease in patients with Thyroglobulin-Elevated Negative Iodine Scintigraphy (TENIS) with spilling sensitivity and specificity to 94.3 percent and 78.4 percent, respectively. It has better sensitivity in detecting metastases that are at a distance particularly that of poorly differentiated and anaplastic thyroid carcinomas where there is reduced avidity to iodine and standard scans are ineffective. Although RAI whole-body scanning is still useful as an initial stage diagnostic procedure and in detection of remnants in differentiated thyroid cancers (DTCs), PET/CT has added accuracy in localizing metabolically active disease especially in follow-up of postoperative patient or in biochemical recurrence when RAI scans are negative. Moreover, it has been seen that 18F-FDOPA PET/CT is more sensitive in enlightening the recurrence of medullary thyroid carcinoma (MTC), particularly in those cases where the level of calcitonin is high in the patients. In general, PET/CT is adding value to the existing imaging protocol because of yielding metabolic information contributing to better staging and planning of the treatment decisions and ultimately in enhancing the overall results of the patient in aggressive/biochemically active thyroid cancers, which do not demonstrate well on conventional modalities. Conclusion: PET/CT scanning exhibits high sensitivity and specificity values in the diagnosis of local recurrence and metastases in post- surgical patients with medullary thyroid carcinoma. Furthermore, based on a comparative analysis of18F-FDG and GA68-DOTATE, it appears that these radiotracers are particularly sensitive and reliable for highlighting MTC, and it was found that there were no statistical differences in terms of sensitivity and specificity. Therefore, these two modalities appear to be complementary in monitoring MTC patients.

Papillary thyroid carcinoma - mixed cystic/solid nodule

2025-06-19

Henry Knipe | Radiopaedia.org

Exploring the Rare Hobnail Variant of Papillary Thyroid Carcinoma: A Case Report

2025-06-18

Fatima Zahra Bouayed , Soufiane Berhili , Mohammed El-Masadi +4 more | Cureus

Sensitivity of a Genomic Sequence Classifier for Diagnosing Medullary Thyroid Carcinoma on Thyroid Fine-Needle Aspiration

2025-06-18

Christine Tran , Lisa Aronson Friedman , Sara L. Zadeh +2 more | JAMA Otolaryngology–Head & Neck Surgery

This case report describes a patient in their 50s with a suspicious thyroid nodule. This case report describes a patient in their 50s with a suspicious thyroid nodule.

Implementation of a Multi‐Gene Molecular Panel at Fine Needle Aspiration Biopsy (<scp>FNAB</scp>) Thyroid Samples: A Compelling Diagnostic and Prognostic Model

2025-06-18

Angeliki Margoni , Kostas A. Papavassiliou , Athanasios G. Papavassiliou | Cytopathology

Application of a multi‐gene panel in FNAB thyroid samples provides a patient‐directed diagnostic and prognostic model. Several genetic mutations and molecular markers are correlated with histological subtypes of thyroid cancer, … Application of a multi‐gene panel in FNAB thyroid samples provides a patient‐directed diagnostic and prognostic model. Several genetic mutations and molecular markers are correlated with histological subtypes of thyroid cancer, revealing the potential role of molecular techniques in targeted therapy. The combination of FNAB and multi‐gene tests introduces clinicians to the benefits of precision oncology.

Efficacy and safety of ultrasound-guided microwave versus radio frequency ablation of benign thyroid nodules

2025-06-18

Nouran Abdelrahman Elghitany , Osama M. Hetta , Mohamed Gamaleldin +1 more | The Egyptian Journal of Radiology and Nuclear Medicine

Abstract Background To compare the two ablation techniques, we assessed 81 benign thyroid nodules of 38 cases who underwent radio frequency ablation (RFA) and 43 cases who underwent microwave ablation … Abstract Background To compare the two ablation techniques, we assessed 81 benign thyroid nodules of 38 cases who underwent radio frequency ablation (RFA) and 43 cases who underwent microwave ablation (MWA) over a 12-month period. The inclusion criteria involved benign thyroid nodules with compression symptoms or cosmetic problems, cytological confirmation of benignity with no atypical cells, and case refusal or unfit for operation. No predilection for the ultrasound nature of the nodules, whether they were cystic, solid, or complex, or their size or number. Radio frequency ablation was carried out utilizing the Mygen (M-3004) radio frequency generator from RF Medical Co., Ltd., South Korea, and microwave ablation (MWA) was conducted utilizing the Canyon KY2000-A MCW generator from Canyon Medical Inc. The clinical problems and the nodules volume have been assessed both following and prior to the surgery. Factors and complications associated with volume reduction rate (VRR) have been assessed. This investigation is designed to evaluate the efficacy and safety of microwave ablation guided by ultrasound (US) versus radio frequency ablation in the management of benign thyroid nodules. Results Mean volume reduction rate (VRR) of MWA group versus the RFA group at one, three, six, and twelve months were 53.1% ± 11.2% versus 45.8% ± 13.5% ( P = 0.009), 67.9% ± 11.5% versus 61.8% ± 12.8% ( P = 0.027), 77.5% ± 9.7% versus 73.4% ± 11% ( P = 0.084), and 85.4% ± 7.6% versus 83.6% ± 6.4% ( P -value = 0.252), respectively. A statistically significant variance has been discovered within the VRR among both the radio frequency ablation group and the microwave ablation group in one- and three-month follow-up. Additionally, all cases were able to maintain thyroid function, and both groups reported a significant reduction in symptom and cosmetic scores. Among the overall case population, one patient in the RF group had a minor burn that resolved after 1 month, and transient voice changes occurred in one patient in each group that resolved after two weeks. Conclusions Both radio frequency ablation and microwave ablation are safe and efficient methods for managing BTNs. The MWA group showed greater volume reduction rates at the 1- and 3-month follow-ups.

Deciphering <scp>EU</scp>‐<scp>TIRADS</scp>: A Pictorial Guide to the Spectrum of Thyroid Nodules

2025-06-18

Thomas Saliba , Charlotte Wynants , Sanjiva Pather +1 more | Sonography

ABSTRACT Thyroid nodules are frequently encountered in clinical practice, with ultrasound playing a central role in their initial evaluation and risk stratification. While most nodules are benign, distinguishing potentially malignant … ABSTRACT Thyroid nodules are frequently encountered in clinical practice, with ultrasound playing a central role in their initial evaluation and risk stratification. While most nodules are benign, distinguishing potentially malignant nodules is important. The EU‐TIRADS classification system, introduced in 2017, offers a simplified framework based on sonographic features such as composition, echogenicity, margins, shape, and echogenic foci. The classification is highly sensitive, with a good negative predictive value, particularly in nodules ≥ 10 mm. Its performance in nodules < 10 mm is less robust. Compared to the American College of Radiology's ACR‐TIRADS, which uses a point‐based system and generally results in fewer fine needle aspirations (FNAs), the use of EU‐TIRADS leads to more biopsies but captures more malignant nodules. Both systems have high sensitivity but modest specificity, with overlap in the features they assess. Key challenges remain, including inter‐observer variability and the interpretation of equivocal features such as vascularity and mild hypoechogenicity. Misleading appearances, often mimicking malignancy due to nodule scarring or retraction, further complicate assessment. While both EU‐TIRADS and ACR‐TIRADS offer valuable frameworks for clinical decision‐making, understanding their limitations and nuances is essential for accurate diagnosis and appropriate management of thyroid nodules. In this paper, we aim to explain thyroid nodule classification systems, with a specific focus on the EU‐TIRADS system.

Papillary Thyroid Microcarcinoma in Thyroid Surgical Practice: Incidental vs. Non-Incidental: A Ten-Year Comparative Study

2025-06-18

Amani Bashir , Mohamed M. El-Zaheri , Ahmad Bashir +4 more | Cancers

With evolving guidelines favoring de-escalation in the management of papillary thyroid microcarcinoma (PTMC), options such as active surveillance and minimally invasive procedures are now considered for patients with low-risk disease. … With evolving guidelines favoring de-escalation in the management of papillary thyroid microcarcinoma (PTMC), options such as active surveillance and minimally invasive procedures are now considered for patients with low-risk disease. However, a subset of PTMCs-particularly non-incidental cases-may exhibit aggressive behavior. This study compares disease characteristics and outcomes between incidental and non-incidental PTMCs over a 10-year period. This is a single-center retrospective comparative analysis utilizing a prospectively collected database of patients referred for thyroid surgery. Papillary thyroid carcinoma accounted for 86.7% of thyroid malignancies, with PTMC comprising 36.2% (137 patients). Incidental PTMC represented 109 out of 1012 patients undergoing surgery for benign thyroid disease (10.8%). Non-incidental PTMC (NIPTMC), diagnosed preoperatively and presenting clinically without coexisting thyroid disease, was identified in 28 patients (20.4%). NIPTMCs were more frequently associated with high-risk features (75% vs. 10.1%, p = 0.004), including extrathyroidal extension (21.43% vs. 7.3% p = 0.0015), positive central lymph nodes (21.43% vs. 2.8%, p = 0.0291), positive lateral lymph nodes (28.6% vs. 0% p = 0.012), and lymphovascular invasion (3.6% vs. 0%). Multifocal PTMC was seen in 37 patients (27%), of which 27 had bilobar disease. Multifocal tumors had a higher likelihood of high-risk features (48.6% vs. 14%, p = 0.007). NIPTMC was a significant predictor of multifocality (p = 0.0098). All patients underwent surgery, none opted for active surveillance. Conclusions: NIPTMC is more often associated with high-risk features and multifocality, necessitating more extensive surgery. These findings emphasize the need for careful preoperative risk stratification to guide individualized management.

A Novel Three-Stage AI-Assisted Approach for Accurate Differential Diagnosis and Classification of NIFTP and Thyroid Neoplasms

2025-06-18

Shweta Birla , Nimisha Tiwari , Pragati Shyamal +5 more | Endocrine Pathology

Oncocytic thyroid carcinoma

2025-06-18

Henry Knipe | Radiopaedia.org

Age- and sex-specific impact on the progression of low-risk papillary thyroid carcinoma under active surveillance: a meta-analysis

2025-06-18

Yang Wang , Liping Wang | Frontiers in Oncology

Background The global incidence of papillary thyroid carcinoma (PTC) is increasing significantly. In response, active surveillance (AS) has been promoted for Low-risk PTC owing to the absence of associated mortality. … Background The global incidence of papillary thyroid carcinoma (PTC) is increasing significantly. In response, active surveillance (AS) has been promoted for Low-risk PTC owing to the absence of associated mortality. However, the association between age, sex, and risk of tumor progression remains unclear. This study aimed to assess the age- and sex-specific Impact on the progression of low-risk PTC. Methods PubMed and Web of Science Core Collection were searched for articles published up to 1 January 2024. Articles reporting patients with PTC undergoing AS were included. Studies involving patients who underwent total or partial thyroidectomy or radiofrequency ablation were excluded. Random- and fixed-effect models were applied to obtain pooled proportions and 95% CIs. Results A total of 972 unique citations were screened and 39 full-text articles were reviewed, including eight cohorts. The mean or median age ranged from 41.5 to 53.1 years, with a predominant inclusion of female patients (76.39%–87.80%). The pooled risk ratio for tumor progression (a growth of 3 mm or more in maximal diameter or lymph node metastasis) in older adults (aged over 30–50 years) compared with younger individuals was 0.58 (95% CI, 0.47–0.71; 4,725 patients, six studies). However, for male patients, the pooled risk ratio for tumor progression compared with female individuals was 1.11 (95% CI, 0.64–1.93; 4,916 patients, six studies). Conclusion This meta-analysis suggests that advanced age may be associated with a lower risk of progression of papillary thyroid microcarcinomas during active surveillance. No significant differences were observed between sexes.

Predictors of early complete nodule shrinkage in symptomatic benign thyroid nodules treated with radiofrequency ablation with or without sclerotherapy: a retrospective study

2025-06-18

Yuxuan Qiu , Tingting Lin , Min Feng +3 more | European Radiology

Molecular predictive biomarker testing in advanced thyroid cancer - a European consensus

2025-06-18

Aleš Ryška , Jaume Capdevila , Matthias S. Dettmer +7 more | European Thyroid Journal

As new precision oncology therapies become available in the thyroid cancer (TC) treatment landscape, appropriate and timely biomarker testing is crucial for treatment selection and requires a multidisciplinary approach. Recently … As new precision oncology therapies become available in the thyroid cancer (TC) treatment landscape, appropriate and timely biomarker testing is crucial for treatment selection and requires a multidisciplinary approach. Recently published European guidelines on advanced/metastatic TC management include a special focus on biomarker testing; however, to date, there remains a need for comprehensive European guidance for standardized molecular testing strategies in TC that encompass a broad set of targetable or potentially targetable alterations, timing of testing, and patients to be tested. This expert opinion article outlines consensus testing algorithms for differentiated TC, medullary TC, and anaplastic TC from a team of endocrinologists, oncologists, molecular biologists, and pathologists to provide standardized recommendations for physicians involved in treating patients with advanced TC. In the differentiated TC algorithm, patients recommended for comprehensive testing by DNA and RNA next-generation sequencing (NGS) include those whose disease has progressed on or is resistant to radioactive iodine treatment. The medullary TC algorithm recommends RET-germline testing for all patients at diagnosis. For patients exhibiting high-risk clinical or pathological features and those whose disease progresses, somatic RET testing with NGS should be discussed and conducted before considering systemic treatment. As anaplastic TC is a highly aggressive disease, molecular reflex testing for BRAF mutations is recommended for all patients at diagnosis, followed by DNA and RNA NGS for those who test BRAF negative. The article also provides consensus recommendations on the use of tumor tissue for testing and on centralization of molecular testing involving multidisciplinary tumor boards.

Neoadjuvant treatment in locally advanced thyroid cancer: a single institution experience

2025-06-17

Lingfeng Xu , Ni Shi , Jun Niu +5 more | Frontiers in Oncology

Background Locally advanced thyroid cancer is a kind of aggressive malignancy with poor overall survival (OS). Neoadjuvant therapy has shown a certain efficacy in locally advanced thyroid cancer. The objective … Background Locally advanced thyroid cancer is a kind of aggressive malignancy with poor overall survival (OS). Neoadjuvant therapy has shown a certain efficacy in locally advanced thyroid cancer. The objective of this study was to assess the efficacy and feasibility of surgery following neoadjuvant therapy in patients. Methods In a retrospective study, we analyzed sixteen patients with locally advanced thyroid cancer from January 2019 to June 2024 in our institution. Among them, 7 patients with unresectable differentiated thyroid cancer (DTC) received tyrosine kinase inhibitors (TKI), and 2 patients with poorly differentiated thyroid cancer (PDTC) and 7 patients with anaplastic thyroid carcinoma (ATC) received a combination therapy of TKI, immune checkpoint inhibitors (ICI) or chemotherapy. Response and progression were evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). OS was calculated using the Kaplan-Meier method. Results 16 (4 male and 12 female) patients with locally advanced thyroid cancer were enrolled in this study, in which 10 patients (62.5%) accepted surgery following neoadjuvant therapy and 6 patients (37.5%) refused surgery. The objective response rate (ORR) was 50.00%, and disease control rate (DCR) was 81.25%. Two partial response (PR), two stable disease (SD) and one progressive disease (PD) patients achieved R0/1 resections after neoadjuvant treatment, resulting in a R0/1 resection rate of 50.00%. Grade III/IV toxicities developed in 2 of 16 patients, requiring dose reduction/discontinuation of TKI. The median OS was 17 months, with one PDTC, four ATC and six DTC patients still alive without relapse. Conclusions Neoadjuvant treatment, including TKI, ICI or chemotherapy treatment, was safe and effective in locally advanced thyroid cancers and could create radical surgery opportunities to improve the prognosis of patients.

Papillary thyroid cancer

2025-06-17

Henry Knipe | Radiopaedia.org

Bleeding Lymph Node Mass in a Postoperative Case of Thyroid Carcinoma: Transarterial Embolization to the Rescue

2025-06-17

Biswajit Sahoo , Arunprakash Pitchaimuthu , Phanindra Kumar Swain +1 more | Cureus

Predicting Risk of Lymph Node Metastasis in Papillary Thyroid Cancer Using miRNAs and Clinicopathological Features

2025-06-17

Penbe Gül Ergün , Çağatay Aydoğan , Ayşe Begüm Ceviz +5 more | Biochemical Genetics

Thyroid-Stimulating Immunoglobulin is not Associated with Aggressive Clinicopathologic Features in Concomitant Graves’ Disease and Papillary Thyroid Cancer.

2025-06-17

Brendan M. Finnerty , Teagan E. Marshall , Chandler A. Annesi +5 more | The American Journal of Surgery

Validation of the Updated Porto Proposal in Papillary Thyroid Microtumors: Analysis of Cases at a University Hospital in Catalonia, Spain

2025-06-17

Karmele Sáez de Gordoa , Elias Tasso , Alexandre Rei +7 more | Cancers

Background/Objectives: Given the high incidence and generally favorable prognosis of papillary thyroid microcarcinomas (PTMs), the Porto Proposal aims to refine the management of these tumors. It designates tumors lacking certain … Background/Objectives: Given the high incidence and generally favorable prognosis of papillary thyroid microcarcinomas (PTMs), the Porto Proposal aims to refine the management of these tumors. It designates tumors lacking certain risk factors as papillary microtumors (PMTs) to avoid overtreatment and reduce patient stress. The updated Porto Proposal (uPp) suggests criteria for reclassifying incidental PTMs as PMTs. This study seeks to validate these criteria using data from a university hospital in Catalonia, Spain, and assess the clinical and pathological characteristics of PTMs. Methods: This retrospective study analyzed patients diagnosed with PTM (≤1 cm) at a university hospital from 2000 to 2024. The study examined variables, including lymph node positivity, incidental diagnosis, tumor location, histological type, treatment, multifocality, age at diagnosis, tumor size, and survival. The uPp criteria were applied to reclassify PTMs into PMTs or PMCs (true papillary microcarcinomas). Student's t-test and chi-square tests were used to evaluate the associations between these variables and the uPp classification. Results: The cohort comprised 107 patients, with 77 (72%) women and 30 men. The mean age at diagnosis was 54.5 years. Out of the total, 77 (72%) cases were reclassified as PMTs and 30 (28%) as PMCs according to the uPp criteria. PMC tumors were larger (mean size 4.5 mm vs. 3.3 mm for PMT, p = 0.014) and were significantly associated with multifocality (52.2%; p = 0.004). Most lymph node-positive cases were classified as PMCs (69.2%; p < 0.001) and were multifocal and bilateral more commonly. However, no significant differences in outcomes between PMCs and PMTs were found (p = 0.188). Follicular histology was significantly more common in PMTs (87.0%, p < 0.001) and rarely had lymph node metastases (4.6%; p = 0.047). Conclusions: The updated Porto Proposal (uPp) effectively identifies PTMs with minimal malignant potential, distinguishing between PMT and PMC. The findings support the protocol's use in reducing unnecessary treatments and psychological stress for patients. The study highlights significant clinical and pathological differences between PTM subtypes, reinforcing the protocol's applicability in daily pathological practice.

Thyroid cancer in West Java: It’s not all papillary and pretty

2025-06-17

Kiki Akhmad Rizki , Rina Kurniasari , Monty Priosadewo +7 more | Cancer Epidemiology

Thyroid cancer is the most common endocrine malignancy in children and adults. The rising incidence of thyroid cancer, which remains poorly understood, raises the need to evaluate whether this increase … Thyroid cancer is the most common endocrine malignancy in children and adults. The rising incidence of thyroid cancer, which remains poorly understood, raises the need to evaluate whether this increase will lead to higher mortality and more aggressive disease. This study aimed to describe the characteristics of thyroid cancer at the largest hospital in West Java and to examine the relationships between these characteristics. This was an observational study. The subjects were patients with thyroid tumors in the oncology surgery division of a tertiary hospital in West Java, Indonesia, from January 2017 to December 2022. A total of 3414 subjects were included in the study. The characteristics of the thyroid tumors were extracted from medical records. The results showed that the mean age of the participants was 47 years, thyroid tumors were more common in women (82.9 %), and tumor location was frequently found on the right side (38.6 %) and over 90 % of cases showed no lymph node metastasis. Univariate analysis confirmed significant associations between histology and patient sex, tumor location, size, and nodal status (all p < 0.05), with very few subcentimeter tumors and higher metastatic rates in papillary (30.3 %) and medullary (37.5 %) carcinomas. Thyroid cancer, particularly papillary thyroid carcinoma, was prevalent in the study population, with significant associations between histopathology, sex, tumor size, and lymph node metastasis. These findings highlight the important of using risk-based FNA and selective surgical referral to exclude low-risk microcarcinomas. Adherence to these strategies will mitigate overdiagnosis and unnecessary surgery.

A machine learning-based model for predicting recurrence in intermediate- and high-risk differentiated thyroid cancer: insights from a retrospective single-center study of 2388 patients

2025-06-17

Yi Li , Zimei Tang , Anwen Ren +5 more | Frontiers in Endocrinology

Purpose Current guidelines provide a recognized yet broad framework for stratifying recurrence risk in differentiated thyroid cancer (DTC) patients. More precise tools are needed for intermediate- and high-risk groups. This … Purpose Current guidelines provide a recognized yet broad framework for stratifying recurrence risk in differentiated thyroid cancer (DTC) patients. More precise tools are needed for intermediate- and high-risk groups. This study aims to identify recurrence-associated risk factors and develop a machine learning-based predictive model. Methods In this retrospective analysis, 2,388 DTC patients were randomly assigned to a training group (1,910 cases) and a validation group (478 cases). Predictive factors were identified using univariate and multivariate analyses. Six machine learning models were trained and validated, with performance evaluated through accuracy, area under the curve, and clinical utility via decision curve analysis. Results Independent risk factors for recurrence included intraglandular dissemination, total tumor size, bilateral cervical lymph node involvement, and Hashimoto’s thyroiditis, while normal/elevated TSH and multifocal nodules were protective. The random forest model demonstrated the best performance (training accuracy: 0.801; validation accuracy: 0.808). A random forest-based online calculator was developed to facilitate individualized risk assessment in clinical settings. Conclusions The random forest model effectively predicts DTC recurrence, offering a practical tool for individualized risk assessment and aiding clinical decision-making.

A Rare Collision in Thyroid and Lymph Node: A Case Report and Review of Literature

2025-06-17

K Gowtham , Suhaildeen Kajamohideen , M Arthi +2 more | Cureus

The Anatomical Relationship Between Intralobar Localization of Papillary Thyroid Carcinoma and Cervical Lymph Node Metastases

2025-06-17

Merve Kucuker , Behice Durgun | Indian Journal of Surgical Oncology

Global, regional, and national trends in thyroid cancer burden (1990-2021): Insights from the GBD 2021 study.

2025-06-16

Ming Tang , Jiarui Li , Manyi Sun +5 more | PubMed

The global incidence of thyroid cancer (TC) has been steadily increasing and is now recognized as one of the most prevalent endocrine malignancies. This study provides a comprehensive evaluation of … The global incidence of thyroid cancer (TC) has been steadily increasing and is now recognized as one of the most prevalent endocrine malignancies. This study provides a comprehensive evaluation of the prevalence, incidence, mortality, and disability-adjusted life years (DALYs) associated with TC from 1990 to 2021. Data for this study were sourced from the 2021 Global Burden of Disease, Injuries, and Risk Factors Study (GBD). To quantify temporal patterns and assess trends in age-standardized TC metrics-namely, age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and DALYs-estimated annual percentage changes (EAPCs) were calculated. The analysis was stratified by sex, 20 age groups, 21 GBD regions, 204 countries/territories, and five Socio-demographic Index (SDI) quintiles. Statistical analyses and plotting were conducted using R statistical software version 4.4.2 and Joinpoint software. The study found that the global burden of thyroid cancer remains substantial, with a significant increase in the total number of cases. In 2021, regions with high SDI reported the highest ASPR, showing an upward trend compared to 1990; however, this trend began to decline significantly after 2009. Conversely, regions with low and low-middle SDI exhibited noticeable increases in ASPR, ASIR, ASDR, and DALYs. The highest prevalence and incidence were observed in the 55-59 age group, followed by a gradual decline. The majority of affected individuals were women. A high body mass index (BMI) was identified as the primary risk factor for TC, and both prevalence and incidence are expected to continue rising through 2040.

The utility of 68Ga-DOTATATE and 18F-FDG PET/CT in predicting the response to tyrosine kinase inhibitors in patients with advanced medullary thyroid cancer

2025-06-16

Eline C. Jager , James W. McNeil , Alexander Papachristos +7 more | Thyroid Research

Assessment of Pediatric Thyroid Nodule Sonographic Features Applying the ACR TIRADS

2025-06-16

Ayman Kushaim , Aqeelah Alsafwani | Journal of Cancer Research Reviews & Reports

FNA is the recommended clinical approach in the conclusive diagnosis of thyroid nodules. ACR TIRADS assess the various criteria considered before performing the FNA/biopsy of any thyroid nodule. Even though … FNA is the recommended clinical approach in the conclusive diagnosis of thyroid nodules. ACR TIRADS assess the various criteria considered before performing the FNA/biopsy of any thyroid nodule. Even though these parameters are validated for adult patients, their use in pediatrics has not been well studied. This research looked in the accuracy of ACR TIRADS in pediatric cases. A retrospective study was done including children who presented with thyroid nodules. Participants were chosen if they were ≤ 14 years and had ultrasound imaging findings of thyroid nodules. Patients were excluded if they had an incidental thyroid nodule detected by other modalities with lack of baseline ultrasound scan, diffuse thyroid disease with no dominant nodule as seen in thyroiditis and Graves’ disease, diffuse heterogeneity, thyroidectomy, and infection/abscess/ phlegmon. 50 thyroid nodules were studied and half were malignant. The ACR TIRADS sensitivity was calculated as 95.8%. Size was also studied to consider its effect on malignancy risk. The research’s findings suggested that ACR TIRADS demonstrates good accuracy level for use in pediatric cases; however, size plays no significant role in the determination of malignancy risk of children’s thyroid nodules.

When the Slide Knows the Sequence: Artificial Intelligence-Assisted Pathology Predicts Mutations in Thyroid Cancer

2025-06-16

C. Christofer Juhlin | Thyroid

POP do “quarto terapêutico” proposto pela equipe profissional aos pacientes com neoplasia de tireoide com Iodoradioativo I-131

2025-06-16

Andrea Cláudia Freitas Ferreira , Arthur de Sá Ferreira | Revista JRG de Estudos Acadêmicos

Objetivo: Analisar os dados da entrevista aos participantes da pesquisa para a confecção do POP, que visar à assistência de qualidade ao paciente com neoplasia de tireoide que utiliza o … Objetivo: Analisar os dados da entrevista aos participantes da pesquisa para a confecção do POP, que visar à assistência de qualidade ao paciente com neoplasia de tireoide que utiliza o “quarto terapêutico” no tratamento com Iodoradioativo I-131. Métodos: Tratou-se de uma pesquisa de campo, com abordagem qualitativa, que utilizou o método Delphi, submetido e aprovado pelo Comitê de Ética e Pesquisa da UNISUAM autorizado com o CAAE: 85530824.6.0000.5235 e Número do Parecer: 7.397.533, o cenário foi o setor de “quarto terapêutico” de um Hospital Universitário Federal do Rio de Janeiro, cujo participante da pesquisa que responderam um questionário no Google Forms. Análise dos dados: Os membros da equipe multidisciplinar, responderam os desafios e responsabilidades ao paciente que é submetido no “quarto terapêutico” no tratamento com Iodoradioativo I-131, que foram suficientes para entender a necessidade e o valor do Procedimento Operacional Padrão. Conclusão: O estudo atendeu ao objetivo proposto e foi possível identificar a necessidade do Procedimento Operacional Padrão, a partir da análise das respostas do questionário.

Thyroid Nodules: Diagnosis and Treatment in Primary Care.

2025-05-30

Jeannine Schübel , Alexander Stahl , Joachim Feldkamp +3 more

Thyroid nodules are very common, with a prevalence of more than 75% among persons over age 60 in Germany, yet more than 80% of them remain asymptomatic and undetected. Only … Thyroid nodules are very common, with a prevalence of more than 75% among persons over age 60 in Germany, yet more than 80% of them remain asymptomatic and undetected. Only a small fraction of thyroid nodules pose a relevant risk to health; these include carcinomas of the thyroid gland (prevalence 0.027%) and functionally autonomous adenomas (clinically relevant prevalence 0.34%). Systematic literature searches based on the PICO scheme or exploratory key questions were carried out during the development of an S3-level clinical practice guideline for the management of patients with thyroid nodules in primary care. The quality of the pertinent guidelines and studies was assessed with standardized instruments. Selected findings are described in this article. Most thyroid nodules are discovered incidentally. Further diagnostic evaluation by the primary care physician is generally only indicated if the patient is symptomatic, has a family history of thyroid cancer, or has a low TSH (thyroid-stimulating hormone) level. Ultrasonography should be performed in targeted and standardized fashion (TIRADS classifications) and cascading diagnostic studies should be avoided. If the nodule is considered potentially malignant, the patient should be referred to a specialist. The indications for treatment include symptoms due to compression, esthetic impairment, or functionally relevant autonomous adenomas. Pharmacotherapy with the goal of shrinking the nodule(s) is now obsolete, and other measures can only be carried out after specialized referral. Rational, patient-centered approaches are needed in primary care so that overdiagnosis and overtreatment can be avoided and appropriate care provided as efficiently as possible. The diagnostic evaluation is focused on the meticulous selection of patients who must be referred to a specialist. For most thyroid nodules, no treatment is indicated.