A comparison of the WHO 2004 and WHO 2017 thyroid tumor classifications.

INTRODUCTION: The category of borderline malignancy or unknown malignant potential was added to the WHO's 2017 classification of thyroid tumours. A new histological variety of papillary tumours and Hurthle cell tumours was given as a separate entity. The classification has also adopted the Turin criteria for histological diagnosis of poorly differentiated cancer (PDC). SETTINGS AND DESIGN: Descriptive study. METHODS AND MATERIAL: From July 2018 to June 2022, 200 thyroid neoplasm patients at a tertiary care facility in western Maharashtra were participated in the prospective research over a period of 4 years. STATISTICAL ANALYSIS USED: The descriptive statistics were used to analyse the collected data. AIM: This study was undertaken to compare the old (2004) and new (2016) WHO classifications and their importance in the treatment of thyroid malignancies. RESULTS: Out of 200 cases, the age range of 31 to 40 years had the greatest number of cases. The ratio of females to males was 5:1. In our study, according to the WHO 2004 classification, malignant tumours comprised 57.5% of the cases, while benign tumours 42.5% of the cases. When tumours were subcategorized, the most frequent benign tumour was follicular adenoma (43.5%) and malignant tumour was papillary thyroid carcinoma (37%). Malignant tumours made up 47.5% of the cases when the tumours were reclassified using the revised WHO 2017 classification, followed by borderline tumours with 27.5% of the cases and benign tumours with 25% of the cases. The most frequent borderline tumour was NIFTP (Noninvasive follicular thyroid neoplasm with papillary-like nuclear features) (17.5%), the most prevalent malignant tumour was papillary carcinoma (including its variant) (32%), and the most frequent benign tumour was follicular adenoma (27%). CONCLUSION: We concluded that the inclusion of the Boderline Category in the new WHO classification significantly improved thyroid cancer management. WHO 2017 classification prevents under diagnosis (in the case of benign tumors) and over diagnosis (in the case of malignant tumors).

Incidental thyroid carcinoma in an endemic goiter area in Italy: histopathological features and predictors of a common finding.

PURPOSE: The occurrence and histopathological features of incidental thyroid carcinoma (ITC) vary considerably among populations from different geographical regions. The aim of this study is to assess the prevalence and histopathological characteristics of ITC in patients who underwent thyroid surgery for apparently benign thyroid diseases in an endemic goiter area in Italy. METHODS: A total of 649 consecutive patients (531 females and 118 males; mean age, 52.9 ± 11.0 years), who underwent thyroid surgery at the Endocrine Surgery Unit of the tertiary care "Renato Dulbecco" University Hospital (Catanzaro, Italy) in the period between years 2017 and 2022, were included in this retrospective study. A comprehensive histopathological examination was performed on surgically excised thyroid tissue. Logistic regression analysis was employed to identify potential predictors of ITC. RESULTS: The histopathological examination revealed the presence of ITC in 81 patients, accounting for 12.5% of the total study population. The female to male ratio was found to be 6.4 to 1. Among the patients with ITC, 72 had papillary carcinoma (PTC), with 53 of these tumors being microcarcinomas (microPTC). Additionally, 5 patients had follicular thyroid carcinoma, 2 patients had low-risk follicular cell-derived thyroid neoplasms, 1 patient had an oncocytic carcinoma, and 1 patient had a medullary thyroid carcinoma. Logistic regression analysis demonstrated a significant association between female sex and incidental microPTC. CONCLUSIONS: These findings provide further evidence of the common occurrence of ITC, typically in the form of microPTC, among individuals who undergo thyroid surgery for apparently benign thyroid diseases.

Prevalence of Differentiated High-Grade Thyroid Carcinoma Among Well-Differentiated Tumors: A Systematic Review and Meta-Analysis.

Background: The current edition of the World Health Organization (WHO) classification of endocrine tumors introduced grading for follicular cell-derived thyroid cancer. Tumors with necrosis and/or high mitotic count but not fulfilling the Turin criteria for poorly differentiated carcinoma will be reclassified as differentiated high-grade thyroid carcinoma (DHGTC). However, the impact of this reclassification has not been evaluated. In this study, we performed a systematic review and meta-analysis to estimate the prevalence of this new entry across thyroid tumor subtypes. Methods: In this systematic review and meta-analysis, studies reporting data on necrosis and/or mitoses in well-differentiated thyroid carcinoma (WDTC) were used to estimate the prevalence of DHGTC. Heterogeneity and potential publication bias were also evaluated. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and quality assessment was performed using a modification of the Newcastle-Ottawa scale. The study has been registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42022378716). Results: In clinically unselected patients, the prevalence of DHGTC in WDTC was 0.072 [95% confidence interval, CI, = 0.045-0.113]. The proportion of high-grade tumors greatly varied across growth patterns and subtypes. Overall, the prevalence of DHGTC was higher in follicular thyroid carcinoma (FTC; 0.146 [CI = 0.101-0.205]) than in papillary thyroid carcinoma (PTC; 0.059 [CI = 0.036-0.097]). Diffuse sclerosing, follicular, and classic subtype PTC had the lowest rates of high-grade features (i.e., 0.018 [CI = 0.004-0.084]; 0.036 [CI = 0.010-0.124]; and 0.042 [CI = 0.027-0.066], respectively), while a greater proportion of solid trabecular and histologically aggressive PTC could be reclassified as DHGTC (i.e., 0.154 [CI = 0.067-0.314] and 0.168 [CI = 0.108-0.252], respectively). Similar proportions were obtained for minimally and widely invasive FTC (i.e., 0.136 [CI = 0.058-0.287] and 0.152 [CI = 0.086-0.254], respectively). Finally, in a cohort of patients with poor prognosis (i.e., fatal cases, metastatic and radioiodine resistant tumors, cases with biochemical recurrence), the proportion of DHGTC was 0.287 [CI = 0.155-0.469]. Conclusions: Following the current WHO indications, some tumors will be reclassified as DHGTC. The proportion of tumors with high-grade features is relevant in FTC, solid trabecular, and histologically aggressive PTC subtypes. A remarkable enrichment in DHGTC among patients with poor prognosis confirms the negative impact of high-grade features on outcome.

Global incidence and prevalence of differentiated thyroid cancer in childhood: systematic review and meta-analysis.

Objective: Differentiated thyroid cancer (DTC) is rare in childhood and adolescence although it represents the most frequent endocrine malignancy in this population. DTC includes both papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). Most pediatric DTCs are PTCs, while FTCs are rare. To date, no systematic reviews on the global epidemiology of pediatric and adolescent DTC have been published. This systematic review and meta-analysis aims to estimate the overall incidence and prevalence of DTCs in patients aged 0-19 years. Methods: The systematic research was conducted from January 2000 to December 2021 through MEDLINE via PubMed, Cochrane Library, and Embase databases. Two separate meta-analyses were performed for PTC and FTC. Results: After the selection phase, a total of 15 studies (3,332 screened) met the inclusion criteria and are reported in the present systematic review. Five studies were conducted in Europe, five in North America, two in South America, one in Asia, one reported data for 49 countries and territories across the five continents, and one from both the USA and Africa. Most of the studies (n = 14) reported data obtained from national registries, and only one provided information collected from hospital medical records. Beyond the actual trend over time, our study reported a pooled global incidence rate (IR) of PTC and FTC in the pediatric age of 0.46 (95% CI: 0.33-0.59) and 0.07 (95% CI: 0.02-0.12) per 100,000 person-years, respectively. The highest IRs were recorded among Caucasian girls, and the lowest in black or other races/ethnicities. Conclusion: Our data confirm that DTC in the pediatric population is a rare condition. The pooled IRs of the studies included in this meta-analysis are ~0.5 for PTC, which is the most common histological type when both genders and all age groups are considered. The implementation of a prospective international registry on pediatric DTC, as part of the wider European Registries for Rare Endocrine Conditions, has been recently proposed. In addition to providing relevant information on the clinical behavior of this rare disease, standardization of data collection will be pivotal to fill current gaps and allow an accurate estimation of the real incidence and risk factors of DTC.

Incidence and Clinicopathological Features of Differentiated High-Grade Thyroid Carcinomas: An Institutional Experience.

Differentiated high-grade thyroid carcinoma (DHGTC) is a new entity in the 2022 WHO classification. We aimed to investigate the incidence and clinicopathological features of differentiated HG thyroid carcinoma (DHGTC) and compare the clinicopathological parameters of DHGTC, DTC without HG features, and poorly differentiated thyroid carcinoma (PDTC). A total of 1069 DTCs including papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs) were included in this study. Consecutive 22 PDTCs were also included for comparative purposes. There were a total of 14 (1.3%) cases of DHGTCs, with 13 HGPTCs (1.2% of PTCs) and one HGFTC (6.7% of FTCs). Compared to DTCs without HG features, DHGTCs were associated with larger tumor size, presence of blood vessel invasion, gross extrathyroidal extension, distant metastasis at the time of diagnosis, higher American Joint Committee on Cancer stage, high American Thyroid Association risk, and TERT promoter mutations. DHGTC and PDTC showed a significantly shorter recurrence-free survival (RFS) than DTC without HG features. Multivariate Cox regression analysis revealed that blood vessel invasion, lateral node metastasis, TERT promoter mutations, and HG features were independent prognostic factors (all p < 0.05). When tumor necrosis and increased mitotic count were evaluated separately, tumor necrosis, but not increased mitotic counts, was found to be an independent prognostic factor (p = 0.006). This study confirmed that DHGTC is significantly associated with aggressive clinicopathological features and poor clinical outcomes, similar to PDTC. Although the incidence is low, careful microscopic examination of HG features in DTC is required.

Evaluation and management of pediatric thyroid nodules and thyroid cancer at a single institution after adoption of the American Thyroid Association 2015 guidelines.

OBJECTIVES: The study purpose is to correlate clinical findings with rates of differentiated thyroid cancer (DTC) in a cohort of children presenting with thyroid nodules at a single institution since the adoption of the 2015 American Thyroid Association (ATA) Guidelines Task Force on Pediatric Thyroid Cancer. METHODS: Clinical, radiographic, and cytopathologic findings were retrospectively analyzed in a pediatric cohort (≤19 years) identified with ICD-10 codes for thyroid nodules and thyroid cancer from January 2017 until May 2021. RESULTS: We analyzed 183 patients with thyroid nodules. The mean patient age was 14 years (interquartile range 11-16) with a female (79.2 %) and white Caucasian (78.1 %) predominance. The overall DTC in our pediatric patient cohort was 12.6 % (23 out of 183). Most of the malignant nodules measured from 1-4 cm (65.2 %) with TI-RADS score of ≥4 (69.6 %). Among the fine-needle aspiration results (n=49), the highest frequency of DTC was within the malignant category (16.33 %), followed by suspicious for malignancy (6.12 %), then atypia or follicular lesion of undetermined significance (8.16 %), and lastly follicular lesion or neoplasm and benign with 4.08 % and 2.04 % respectively. Of the forty-four thyroid nodules that underwent surgical intervention, pathology was remarkable for 19 papillary thyroid carcinoma (43.18 %) and 4 follicular thyroid carcinoma (9.09 %). CONCLUSIONS: Based on the analysis of our pediatric cohort in the southeast region at a single institution, adoption of the 2015 ATA guidelines could lead to an increased accuracy in detecting DTC while reducing the number of patients requiring interventions, such as FNA biopsy and/or surgeries. Further, based on our small cohort, it would be reasonable for thyroid nodules 1 cm or less to be monitored clinically with physical exam and ultrasonography, with further therapeutic or diagnostic intervention considered based on concerning features or parental shared decision making.

Thyroid cancers in children and adolescents in France: Incidence, survival and clinical management over the 2000-2018 period.

INTRODUCTION: Thyroid cancer is the first cause of endocrine malignancy among children. Over the past decades, an increase in the incidence rates (IR) has been observed around the world. Our study aimed to describe epidemiology, therapeutic management and survival rates of children and adolescents with thyroid cancer in France. METHODS: A population-based study was conducted between 2000 and 2018 in children and adolescents less than 17 years with a diagnostic of thyroid cancer. RESULTS: A total of 774 thyroid cancers were included: 579 papillary (PTC), 83 follicular (FTC), and 111 medullary carcinomas (MTC). PTC are more frequent in females and in adolescents whereas MTC mainly concerned children, mostly with a familial predisposition. Almost all patients underwent thyroidectomy, completed for most patients with PTC and FTC by radioiodine therapy. Cervical dissection was performed more frequently in patients having PTC and MTC compared to those with FTC. Between 2000 and 2018, thyroid cancers IR in children fluctuated between 1.3 and 3.2 per million, without any significant trend. The median follow-up time was 11.3 years in children, and 5.7 years in adolescents. The 5year-OS was greater than 98.5%. CONCLUSIONS: Population-based studies are crucial for better understanding and delineation of best management of rare diseases as thyroid cancers in pediatric and adolescent population. Considering the very favorable survival, a stratification should be proposed between cases at low risk and cases at high risk of relapse, in order to consider a strategy of therapeutic de-escalation in the most favorable cases.

Variation in the Diagnosis of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features.

CONTEXT: Noninvasive encapsulated follicular variant of papillary thyroid cancer was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in January 2017. The impact of this nomenclature change at a population level remains unknown. OBJECTIVE: Examine use of NIFTP across different US regions and populations. DESIGN: Descriptive epidemiology study using SEER-22 data (2000-2019). PARTICIPANTS: Individuals diagnosed with papillary or follicular thyroid cancer (2000-2019) or NIFTP (2017-2019). MAIN OUTCOME MEASURES: Annual incidence rates of thyroid cancer by subtype and NIFTP. Using 2018-2019 data, (1) rates of NIFTP at the 17 SEER-22 sites and (2) comparison of demographics for patients diagnosed with NIFTP vs papillary and follicular thyroid cancer. RESULTS: NIFTP comprised 2.2% and 2.6% of cases in 2018 and 2019, respectively. Between 2018 and 2019, large heterogeneity was observed in the regional use of NIFTP diagnosis, with site-specific incidence rates between 0.0% and 6.2% (median 2.8%, interquartile range 1.3-3.6%). A diagnosis of NIFTP (vs papillary and follicular thyroid cancer) in 2018 and 2019 was significantly associated with older age (P = 0.012 and P = 0.009, respectively), Black race (both Ps < 0.001), and non-Hispanic ethnicity (both Ps < 0.001). CONCLUSIONS: Marked variation exists in the use of the NIFTP diagnosis. The recent 2021 coding change that resulted in NIFTP, a tumor with uncertain malignant potential and for which there is no long-term outcome data available, no longer being a reportable diagnosis to SEER will disproportionately affect vulnerable patient groups such as older patients and Black patients, in addition to patients who reside in regions with higher rates of NIFTP diagnoses.

Non-invasive follicular neoplasm with papillary-like nuclear features: a challenging and infrequent entity in Argentina.

PURPOSE: Non-invasive encapsulated follicular variant of papillary thyroid cancer was reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). These neoplasms have an extremely low malignant potential. The aim of this study was (1) to assess the prevalence of NIFTP in patients with papillary thyroid carcinoma, (2) to evaluate their outcomes, and (3) to determine their molecular profile. METHODS: Multicenter, descriptive, retrospective study. Patients with papillary thyroid cancer diagnosed from January 2006 to December 2016 from 11 referral centers were included. Diagnosis of NIFTP was based on criteria described by Nikiforov et al. in 2018. At least two pathologists agreed on the diagnosis. Two thousand six hundred and seventy-seven papillary thyroid cancer patients were included; 456 (17%) of them were follicular variant papillary thyroid cancer, and 30 (1.12%) fulfilled diagnostic criteria for NIFTP. RESULTS: Each of the 30 included patients underwent a total thyroidectomy, and 50% were treated with radioiodine (median dose 100 mCi). After a median follow-up of 37 months, 84% of patients had an excellent response, 3% had an indeterminate response and data was missing in the remaining 13%. No metastatic lymph nodes, distant metastases or recurrences were found. RAS mutations were detected in 4 patients (13%). CONCLUSION: The prevalence of NIFTP in our series is amongst the lowest reported. Excellent outcomes of patients underscore their low malignant potential. Molecular findings differ from other series, probably related to environmental or ethnic features of our population and the meticulous criteria for diagnosing NIFTP.

Large, Slowly Growing, Benign Thyroid Nodules Frequently Coexist With Synchronous Thyroid Cancers.

CONTEXT: Thyroid nodules' size should not be the sole criterion for thyroidectomy; however, many patients undergo surgery for large or slowly growing nodules. OBJECTIVE: We evaluated risk for clinically significant thyroid cancer in patients with large or slowly growing nodules. METHODS: We reviewed data from 2 prospectively collected databases of patients undergoing thyroidectomies in tertiary referral centers in the USA and Greece over 14 consecutive years. We collected data on the preoperative surgical indication, FNA cytology, and surgical pathology. We included subjects operated solely for large or growing thyroid nodules, without any known or presumed thyroid cancer or high risk for malignancy, family history of thyroid cancer, or prior radiation exposure. RESULTS: We reviewed 5523 consecutive cases (USA: 2711; Greece: 2812). After excluding 3059 subjects, we included 2464 subjects in the present analysis. Overall, 533 thyroid cancers were identified (21.3%): 372 (69.8%) microcarcinomas (<1 cm) and 161 (30.2%) macrocarcinomas (≥1 cm). The histology was consistent with papillary cancer (n = 503), follicular cancer (n = 12), Hürthle cell cancer (n = 9), medullary cancer (n = 5), and mixed histology cancers n = 4. Only 47 (1.9%) of our subjects had any form of thyroid cancer in the nodule that originally led to surgery. The cancers were multifocal in 165 subjects; had extrathyroidal extension in 61, capsular invasion in 80, lymph node involvement in 35, and bone metastasis in 2 subjects. CONCLUSION: The risk of synchronous, clinically important thyroid cancers is small, but not null in patients with large or slow growing thyroid nodules. Therefore, more precise preoperative evaluation is needed to separate the patients who would clearly benefit from thyroid surgery from the vast majority of those who do not need to be operated.

Evaluating the use of a two-step age-based cutoff for the UICC/AJCC TNM staging system in patients with papillary or follicular thyroid cancer.

BACKGROUND: The joint Union International Contre le Cancer and American Joint Committee on Cancer (UICC/AJCC) Tumor, Node, Metastasis (TNM) staging system for differentiated thyroid cancer (DTC) involves a single age cutoff as a prognostic criterion. Because a single cutoff is a dichotomization of what might be a sliding scale, using multiple age cutoffs might result into a better stage definition. The aim of our study was to investigate if using a two-step age-based cutoff would improve the TNM staging system regarding disease-specific survival (DSS). METHODS: We retrospectively studied two cohorts of adult DTC patients from The Netherlands and Germany. DSS was analyzed for papillary (PTC) and follicular thyroid cancer (FTC) separately, investigating several two-step age-based cutoffs for those with distant metastases; below lower threshold classified as stage I, between lower and upper threshold as stage II, and above upper threshold as stage IV. RESULTS: We included 3074 DTC patients (77% PTC). For PTC, an age cutoff of 45 with 50 years had the best statistical model performance, while this was 25 with 40 years for FTC. However, differences with the optimal single age cutoffs of 50 years for PTC and 40 years for FTC were small. CONCLUSIONS: The optimal two-step age-based cutoff to predict DSS is 45 with 50 years for PTC and 25 with 40 years for FTC, rather than 55 years currently used for DTC. Although these two-step age-based cutoffs were marginally better from a statistical point of view, from a clinical point of view, the recently defined optimal single age cutoffs of 50 years for PTC and 40 years for FTC might be preferable.

Thyroid cancer incidence and trends by demographic and tumor characteristics in Oran, Algeria: 1993-2013, a population-based analysis.

OBJECTIVES: Incidence rates of thyroid cancer have dramatically increased over recent decades in many countries, particularly the papillary histotype and microcarcinomas. We examined thyroid cancer incidence and trends by demographic and tumor characteristics based on 1443 patients with thyroid cancer diagnosed between 1993 and 2013 in Oran district, in Northwest Algeria. METHODS: All thyroid cancer cases were abstracted from medical records and pathology reports and classified according to the International Classification for Diseases in Oncology, third edition. Age-specific, age-standardized incidence rates per 100 000 person-years, and annual percent changes (APC) in the incidence were calculated. RESULTS: Age-standardized incidence was 11.7 per 100 000 for women and 2.0 per 100 000 for men. Thyroid cancer incidence increased over time significantly in women (APC: +3.72%; P < 0.05), mostly due to an increased incidence of the papillary histotype (APC: +5.48%; P < 0.05), and microcarcinomas (APC: +17.34%; P < 0.05). During the same time period, the incidence of follicular thyroid carcinomas decreased (APC: -3.74%; P < 0.05). CONCLUSIONS: The results of our study showing an upward trend of thyroid cancer incidence driven largely by increases in the papillary histotype are consistent with previous studies. The higher increase has coincided with the introduction of fine needle aspiration and thyroid ultrasound in the 1990s, and may have led to overdiagnosis. However, the increased papillary-to-follicular ratio observed over time is possibly a late effect of iodine supplementation implemented in Algeria in 1967 to combat endemic goiter. Further larger-scale population-based research is needed to gain insight into thyroid cancer etiology.

Risk Patterns of Distant Metastases in Follicular, Papillary and Medullary Thyroid Cancer.

This study of 542 patients with follicular thyroid cancer, 366 patients with the follicular variant and 1452 patients with the classical variant of papillary thyroid cancer, and 819 patients with sporadic medullary thyroid cancer operated at a tertiary referral center aimed to determine risk patterns of distant metastasis for each tumor entity, which are ill-defined. On multivariable logistic regression analyses, lymph node metastasis consistently emerged as an independent risk factor of distant metastasis, yielding odds ratios (ORs) of 2.4 and 2.8 for follicular thyroid cancer and the follicular variant of papillary thyroid cancer, and ORs of 5.9 and 6.4 for the classical variant of papillary thyroid cancer and sporadic medullary thyroid cancer. Another independent risk factor consistently associated with distant metastasis, most strongly in follicular thyroid cancer and the follicular variant of papillary thyroid cancer (OR 3.5 and 4.0), was patient age >60 years. Altogether, 2 distinct risk patterns of distant metastasis were identified, which were modulated by other cancer type-dependent risk factors: one with lymph node metastasis as leading component (classical variant of papillary thyroid cancer and sporadic medullary thyroid cancer), and another one with age as leading component (follicular thyroid cancer and the follicular variant of papillary thyroid cancer). Distant metastasis was exceptional in node-negative patients with sporadic medullary thyroid cancer (1.7%) and the classical variant of papillary thyroid cancer (1.4%), and infrequent in node-negative patients with the follicular variant of papillary thyroid cancer (4.4%). These findings delineate windows of opportunity for early surgical intervention before distant metastasis has occurred.

Incidence and dynamic risk stratification in differentiated thyroid cancer in a high-resolution clinic, 2002-2017.

OBJECTIVE: We evaluated the incidence, progression and the dynamic risk stratification in differentiated thyroid cancer (DTC) under follow-up in a high-resolution clinic (HRC). METHODS: This was a retrospective observational study on incident cases in the tumor registry from 2002 to 2017 and their evolution under follow-up in HRC. RESULTS: A total of 444 patients (78.5% women, 52.1±14.9 mean years old) were DTC diagnosed from 2002 to 2017. The incidence rate of DTC increased from 5.2 to 25.7×105 habitants/year in women and from 2.3 to 7.1×105 habitants/year in men (P<0.0001). This increased incidence was not associated with an increment in the incidental papillary microcarcinoma diagnosed (from 29.4% to 32%). In those patients undergoing follow-up at the HRC (84% papillary carcinomas), 65.7% were classified as being at a low risk of recurrence compared to 14.5% at high risk. Of those, 88.8% classified as making an excellent response at diagnosis remained disease-free at the final follow-up visit. However, those patients with an indeterminate or structurally incomplete response at diagnosis evolved to an excellent response in 55.8% and 42.9% of the cases, respectively, compared to 14.8% of those with a biochemically incomplete response (P<0.001) CONCLUSIONS: The increased incidence of DTC is similar to results published previously in other countries. Dynamic risk stratification systems adequately classify DTC patients and assess diagnostic and treatment procedures, especially in low-risk subgroups.

Malignancy Rate of Bethesda Class III Thyroid Nodules Based on the Presence of Chronic Lymphocytic Thyroiditis in Surgical Patients.

Background: Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis (CLT), may interfere with the accurate cytological diagnosis of thyroid nodules. Recently, HT has been considered a premalignant condition for thyroid cancer development. The diagnosis of atypia of undetermined significance/follicular lesions of undetermined significance (AUS/FLUS) thyroid nodules is challenging and evidence for the malignancy risk of AUS/FLUS thyroid nodules coexisting with CLT is scarce. Therefore, we assessed the malignancy risk of AUS/FLUS thyroid nodules according to the presence of background CLT. Methods: This study included 357 surgically resected thyroid nodules with AUS/FLUS cytology. Cases with concomitant malignant nodules were excluded. CLT was defined based on the pathologic report after thyroid surgery. Results: Among 357 tumors, 130 tumors (36%) were confirmed to have coexisting CLT, and 170 tumors (48%) were determined to be malignant after thyroidectomy. Malignancy rates were similar in both groups (48% in each) regardless of background CLT (62/130 with CLT vs. 108/227 without CLT). In the group with CLT, thyroiditis was more frequent in the final pathology (12% with CLT vs. 1% without CLT, P = 0.003). In multivariate analysis, positive BRAFV600E mutation, highly suspicious sonographic features (K-TIRADS 5), and smaller thyroid nodules were significant factors for thyroid malignancies. Conclusion: The malignancy rate of thyroid nodules with AUS/FLUS cytology was comparable irrespective of the presence of underlying CLT.

Association of total cholesterol and atherosclerotic cardiovascular disease in patients with follicular thyroid cancer: A real-world study from Chinese populations.

ABSTRACT: The association between serum total cholesterol (TC) level and incident atherosclerotic cardiovascular disease (ASCVD) in patients with follicular thyroid cancer postthyroidectomy is unknown.This was a retrospective study and patients (n = 384) were divided into low and high TC groups according to the median TC level. Incidence of composite ASCVD (myocardial infarction, ischemic stroke, and cardiovascular death) was compared between these 2 groups and factors contributing to the association of TC and ASCVD were evaluated.Patients in the high TC group were older and more likely to have diabetes and have higher C-reactive protein level. After thyroidectomy, serum levels of free triiodothyronine and free thyroxine were lower while thyroid-stimulating hormone level was higher in the high TC group. 31.6% and 39.7% of patients developed hypothyroidism in the low and high TC groups (P < .05) postthyroidectomy. The incidence rate of composite ASCVD was higher in the high TC versus low TC groups, with incidence rate ratio of 1.69 (95% confidence interval [CI]: 1.07-2.69), which was mainly driven by a higher incidence rate of myocardial infarction in the high TC group (incidence rate ratio: 2.11 and 95% CI: 1.10-4.20). In unadjusted model, higher TC was associated with 73% higher risk of composite ASCVD. After adjustment for hypothyroidism, the association of higher TC and composite ASCVD was attenuated into insignificance, with hazard ratio of 0.92 and 95% CI: 0.81 to 1.34.Increased TC level was associated with composite ASCVD, which might be attributed to hypothyroidism postthyroidectomy. The use of levothyroxine might help to prevent hypercholestemia and reduce the incidence of ASCVD.

Thyroid cancer in the Democratic Republic of the Congo: Frequency and risk factors.

BACKGROUND: The prevalence of thyroid cancer is increasing steadily in most countries, partly due to better, earlier diagnosis. However, there is little data for developing countries, where the technical platform is often very limited, especially in Africa. OBJECTIVES: To assess the frequency of thyroid cancer in the Democratic Republic of the Congo (DRC) and to analyze the epidemiological, clinical, and ultrasound risk factors. MATERIAL AND METHODS: This is a multicenter cross-sectional study of 594 patients operated on for a thyroid mass from 2005 to 2019, in 35 centers in the DRC and for whom histopathological analyses were performed. RESULTS: The frequency of thyroid cancers in our cohort was 20%, mostly in patients over the age of 40 (62% of patients). These cancers were mainly diagnosed at the clinical stage, due to the presence of palpable masses. Papillary cancer was the most common (67.2% of patients), followed by follicular cancer (28% of cases). We found a high prevalence of anaplastic cancer (7.6%). These frequencies are probably the consequence of the fact that histopathological analyses are not systematically performed in the DRC, but mostly on tissues that the thyroid surgeons suspect to be malignant. Age ≥60 years, the presence of adenopathies upon palpation or on ultrasound, the solid nature and hypoechogenicity of nodules, the presence of macronodules and calcifications were the factors independently associated with the diagnosis of cancer in the study population. CONCLUSIONS: In this first study performed in the DRC, we have found that thyroid cancer is common. It is mainly detected at clinical stages, with patients over the age of 40 years and women being the most affected. The histopathology distribution differs from that in developed countries, with a lower prevalence of papillary cancer and a higher prevalence of the anaplastic type. In developing countries, it appears necessary to introduce the use of more precise diagnostic tools for thyroid cancer and also, to reinforce the improvement of known, controllable risk factors such as iodine deficiency.

Outcomes of repeat fineneedle aspiration biopsy for AUS/FLUS thyroid nodules.

OBJECTIVE: To determine the proportion of aspirates reclassified into each Bethesda category and to assess the rates of malignancy in each of them on repeat fine-needle aspiration biopsy (RFNA) following an AUS/FLUS diagnosis. DESIGN: Systematic review and meta-analysis. METHODS: On February 2019, Pubmed/MEDLINE, EMBASE, WoS, and the Cochrane Library were searched for articles published from January 1, 2007. All studies published in English describing RFNA outcomes in AUS/FLUS nodules were included. PRISMA and MOOSE guidelines were followed. Five investigators independently assessed the eligibility of the studies. Two investigators extracted summary data and assessed the risk of bias. Data were pooled using a random-effects model. The rate of malignancy was calculated on resected nodules only (upper limit of true value); and considering all unresected nodules were benign (lower limit of true value). The protocol was registered in PROSPERO (CRD42019123114). RESULTS: Of 2937 retrieved studies, 27 were eligible. The meta-analysis was conducted on summary data of 3932 AUS/FLUS thyroid nodules with RFNA. RFNA cytology would reclassify into categories I through VI of Bethesda: 4% (3%, 5%), 48% (43%, 54%), 26% (20%, 32%), 4% (3%, 6%), 5% (3%, 6%), and 2% (1%, 2%) of AUS/FLUS nodules. Malignancy rates of resected nodules were 24% (9%, 38%), 4% (1%, 7%), 40% (28%, 52%), 37% (27%, 47%), 79% (69%, 90%), and 99% (95%, 100%) for categories I through VI of Bethesda. There was high heterogeneity in these data. CONCLUSIONS: RFNA reclassified two-thirds of the AUS/FLUS specimens into a more definitive cytological category, with a benign call rate of nearly 50% and a negative predictive value greater than 96%.

The Incidence of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: A Meta-Analysis Assessing Worldwide Impact of the Reclassification.

Background: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) reclassification has significantly influenced the field of thyroidology. However, the extent of this impact depends upon the incidence of NIFTP in a given population. In this meta-analysis, we aimed to obtain robust information about the actual incidence of NIFTP worldwide by reviewing the published data. Methods: Comprehensive literature search was performed using electronic databases of PubMed and Web of Science over a five-year period (January 1, 2016, to January 30, 2021). The incidence of NIFTP was calculated by dividing the number of NIFTPs by the number of papillary thyroid carcinomas (PTCs). Meta-analysis of proportion and their 95% confidence interval [CI] were pooled using the random-effect model. Heterogeneity across the included studies was assessed using I2 statistics. Egger's regression test and funnel plot of estimates were used to evaluate the publication bias. p-Value <0.05 was considered significant. Results: From 505 publications, we included 50 studies, all retrospective, with 100,780 PTCs and 3990 NIFTP from 92 institutions worldwide. The overall incidence of NIFTP was 6.0% [CI 4.4-8.2] among PTCs or thyroid malignancies with a high level of heterogeneity among the included studies (I2 = 98.6%). NIFTP incidence was largely similar in North America and Europe (9.3% vs. 9.6%), with a significantly lower overall rate in Asia (2.1%). There was a significant decline in the reported incidence of NIFTP in non-Asian studies published after 2017 (p = 0.002). On applying our data on global thyroid cancer statistics, this reclassification would affect ∼30,881 patients annually, with a lower impact in Asia compared with North America and Europe. Conclusions: This comprehensive meta-analysis confirms that the worldwide NIFTP incidence is much lower than estimated initially. The NIFTP rates are significantly lower in Asian compared with North American and European countries. Apart from geography, NIFTP rates are significantly influenced by the nature of study, type of database used for sample collection, and the diagnostic criteria used. Introduction of NIFTP may potentially spare over 30,000 patients worldwide annually from clinical and psychological consequences of a thyroid cancer diagnosis.

Decreasing trends in thyroid cancer incidence in South Korea: What happened in South Korea?

BACKGROUND: South Korea has the highest incidence of thyroid cancer in the world. Our study examined the trends in thyroid cancer incidence by the histologic type, cancer stage, and age group and explored possible factors that affected thyroid cancer trends. METHODS: We conducted a descriptive epidemiological study using the national cancer registry data and cause of death data from 1999 to 2016 in South Korea. Age-standardized rates were calculated using Segi's world standard population. Joinpoint regression analysis was applied to determine the changing point of thyroid cancer trends according to histologic type; Surveillance, Epidemiology, and End Results (SEER) summary stage; and age groups by sex. RESULTS: The age-standardized incidence of thyroid cancer in both men and women increased from 6.3 per 100,000 people in 1999 to 63.4 per 100,000 in 2012 but declined from 2012 to 2016, before the debates for over diagnosis of thyroid cancer began in 2014. The age-standardized mortality rate of thyroid cancer, incidence of distant thyroid cancer, and incidence of regional and localized thyroid cancer started to decline since early 2000, 2010, and 2012, respectively. In addition, thyroid cancer prevalence in thyroid nodules showed decreasing trends from 1999-2000 to 2013-2014. CONCLUSIONS: The incidence of thyroid cancer began declining from 2012, before the debates for over diagnosis of thyroid cancer began in 2014. Changes in guidelines for thyroid nodule examinations may have affected this inflection point. Moreover, the debates for over diagnosis of thyroid cancer may have accelerated the decline in thyroid cancer.