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The incidence of thyroid cancer has shown marked increases globally over recent decades. This study investigated how the incidence of papillary thyroid carcinoma (PTC) subtypes and World Health Organisation (WHO) endocrine tumour classification changes have affected overall thyroid cancer incidence recorded in Australia. Using incidence data from the Australian Institute of Health and Welfare cancer registry (spanning 1982 to 2019), this descriptive epidemiological study employed joinpoint regression analysis to assess temporal trends in thyroid carcinoma incidence, focusing on PTC. Results were then compared with WHO endocrine tumour classification changes over the same period. The results showed increasing trends for the classic PTC subtype over the entire 38-year period and for thyroid microcarcinomas post-2003, while a declining trend for the follicular variant of PTC was observed commencing in 2015. Examination of PTC incidence also revealed distinct changes in trends that align with the WHO classification of papillary microcarcinoma as a subtype in 2004 and the reclassification of some encapsulated follicular variant of PTCs to non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) in 2016/17. Even when taking these WHO classification changes into account, significant increases in PTC over the last three decades are observed. These findings underscore the shifts in classification driven by improving diagnostic clarity influencing thyroid carcinoma incidence patterns. However, thyroid carcinoma cases in Australia have dramatically increased over the last three decades independent of WHO classification changes, suggesting a genuine increase rather than simply being a direct consequence of improved reporting and diagnostics., Competing Interests: Declarations. Ethics approval and consent to participate: Griffith University, Office for Research, Human Research Ethics approved Ethical Clearance (GU Ref No: 2024/007). Consent for publication: All authors consent for publication. Competing Interests: The authors declare no competing interests., (© 2025. The Author(s).)

Context: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported., Objective: To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions., Methods: Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey., Results: A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania., Conclusion: Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is increasingly being diagnosed incidentally on imaging. It has malignant potential, making it vital to establish the correct diagnosis, assess its malignant risk and follow a management strategy to prevent development of invasive carcinoma of the pancreas., Objective: This review focuses on the epidemiology, natural history, risk factors, diagnosis and management of IPMN of the pancreas, and will provide practical points for general practitioners., Discussion: IPMN of the pancreas can transform into invasive pancreatic carcinoma at a low rate of approximately 2%/year. Upon diagnosis of IPMN, it is risk stratified based on the presence of worrisome or high-risk stigmata, which guides further management. Management needs to be individualised based on IPMN and patient factors due to limitations with the current diagnostic tools.

Thyroid cancer more commonly affects women than men and is the third most frequently diagnosed cancer among women of reproductive age. We conducted a nested case-control study within the Finnish Maternity Cohort to evaluate pre-diagnostic sex steroid and thyroid function markers in relation to subsequent maternal papillary thyroid cancer. Cases (n = 605) were women ages 18-44 years, who provided an early-pregnancy (<20 weeks gestation) blood sample and were diagnosed with papillary thyroid cancer up to 11 years afterward. Controls (n = 1185) were matched to cases 2:1 by gestational age, mother's age, and date at blood draw. Odds ratios (ORs) for the associations of serum thyroid peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab), thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), progesterone, and estradiol with papillary thyroid cancer were estimated using conditional logistic regression. TPO-Ab and Tg-Ab positivity (>95th percentile among controls) were associated with more than 3-fold (OR = 3.32, 95% confidence interval [CI] 2.33-4.72) and 2-fold (OR = 2.03, 95% CI 1.41-2.93) increased odds of papillary thyroid cancer, respectively. These associations were similar by time since blood draw, parity, gestational age, smoking status, and age and stage at diagnosis. In models excluding TPO-Ab or Tg-Ab positivity, TPO-Ab (quartile 4 vs. 1: OR = 1.66, 95% CI 1.17-2.37, p-trend = .002) and Tg-Ab (quartile 4 vs. 1: OR = 1.74, 95% CI 1.22-2.49, p-trend = .01) levels were positively associated with papillary thyroid cancer. No associations were observed for estradiol, progesterone, TSH, fT3, or fT4 overall. Our results suggest that thyroid autoimmunity in early pregnancy may increase the risk of maternal papillary thyroid cancer., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Purpose: The current management guidelines for low-risk papillary thyroid microcarcinoma (PTMC) do not specify how to screen for growing tumors. We sought to explore the possible risk factors for tumor enlargement in patients with low-risk PTMC under active surveillance (AS)., Methods: We searched the PubMed and Embase databases for high quality studies up to January 10th, 2024. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies, and Review Manager 5.4 was used to analyze possible risk factors and calculate pooled risk ratios (RRs) via the inverse-variance calculation method., Results: Eleven studies were included in our meta-analysis. Among the 8880 participants, 464 experienced tumor growth, and the incidence of tumor growth varied from 3.4% to 19.4%. The results of the meta-analysis showed that tumor enlargement was associated with younger age (pooled RR = 2.32, 95% CI = 1.85-2.90, p < 0.00001; 8 studies), and higher serum thyroid-stimulating hormone (TSH) levels (pooled RR = 2.28, 95% CI = 1.19-4.37, p = 0.01; 6 studies), and could be related to pregnancy (pooled RR = 2.54, 95% CI = 1.17-5.52, p = 0.02; 2 studies). However, these following factors showed no significant association with tumor growth: sex (pooled RR = 1.07, 95% CI = 0.63-1.84, p = 0.79; 7 studies), tumor size at diagnosis (pooled RR = 1.08, 95% CI = 0.63-1.85, p = 0.77; 5 studies), and Hashimoto's thyroiditis (HT) (pooled RR = 1.56, 95% CI = 0.93-2.60, p = 0.09; 2 studies)., Conclusion: Our analysis identified that younger age and higher serum TSH levels were higher risk factors for tumor enlargement in low-risk PTMC patients. Pregnancy is a suspected risk factor., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Confidence in long-term treatment results of radiofrequency ablation (RFA) for papillary thyroid microcarcinoma (PTMC) is required in comparison with surgery and active surveillance (AS). The objective of this meta-analysis is to report more than three years of follow-up results of radiofrequency ablation for PTMCs., Methods: Ovid PUBMED, COCHRANE, and EMBASE databases were searched through Nov 19, 2023, for studies reporting outcomes in patients with PTMC treated with radiofrequency ablation and followed up for more than 3 years. The standard mean difference of the tumor volume before and after therapy, tumor recurrence, lymph node (LN) metastasis, distant metastasis, complications, and the pooled volume reduction rates (VRRs) at 1, 3, 6, 12, 24, 36, and 48 months after radiofrequency ablation were assessed. Data were extracted and methodological quality was assessed independently by two radiologists according to the PRISMA guidelines., Results: Eight studies, involving 2131 patients, met the inclusion criteria through database searches. The overall VRR was 99.81 % (95 % CI: 99.68, 99.95) in the last follow-up. During a mean pooled follow-up of 46.59 months, 69 patients experienced local PTMC recurrence, with 8 cases within the ablation area. Additionally, 44 patients were diagnosed with newly discovered PTMC, and 17 patients exhibited lymph node metastases. Among the patients with PTMC recurrence, 3 were under active surveillance while 59 underwent additional RFA. The pooled mean complication rate was 2.80 %, with no instances of life-threatening or delayed complications., Conclusions: Radiofrequency ablation proves to be an effective local tumor control method for low-risk PTMC patients, resulting in clinically significant and enduring volume reduction. The rate of regrowth and retreatment requirement post-RFA was notably lower, positioning RFA as a compelling alternative to existing treatment options., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Bladder cancer is the ninth leading cause of death worldwide and 14th leading cause of death in Pakistan. The objective of this study was to determine the frequency of urothelial carcinoma in various age groups, its gender distribution, and grades. A total of 131 cases of urothelial carcinoma, received at Department of Pathology, Peshawar Medical College, Peshawar, between January 2017 to December 2022, were included in the study; of them 107 (81.6%) were males while 24 (18.3%) were females with a mean age of 62±13 years. The most common histological subtype was papillary urothelial carcinoma in 117(89.3%) cases, followed by Squamous and Glandular in 5(3.8%) cases. Majority of the urothelial carcinoma with high grade showed a statistically significant relation with muscle invasion 38 (50.66%). Males were four times more likely to have urothelial carcinoma while older age groups were more likely to have high grade urothelial carcinoma.

Objective: Papillary thyroid carcinoma, per se, is the most common type of thyroid cancer, and Hashimoto's thyroiditis is the most frequent autoimmune disease of the papillon gland. The liaison between Hashimoto's thyroiditis and thyroid cancers is still an ongoing debate in thyroidology. The aim of the study was to discuss the frequency of the co-occurrence of Hashimoto's thyroiditis and papillary thyroid carcinoma., Methods: This study is designed as a retrospective analytical cohort study. The institutional database and archive of histopathology scanning identified the patients who had undergone thyroidectomy between January 2022 and January 2016. The Statistical Package for Social Sciences v21.0 program was used for statistical purposes. Descriptive and chi-square tests were applied, and a p<0.05 was considered significant., Results: Of 498 patients who had undergone thyroidectomy for 4 years, 99 (20%) were male and 399 (80%) were female. Of note, papillary thyroid carcinoma was revealed in 160 (32%) patients, and Hashimoto's thyroiditis was recognized in 178 (35.74%) patients. The prevalence of Hashimoto's thyroiditis in cases with papillary thyroid carcinoma was 43.8%, while the prevalence in patients with Hashimoto's thyroiditis was 41.1%., Conclusion: A debate still remains on the propriety of these two phenomena. Herewith, we recognized a correlation between the presence of papillary thyroid carcinoma and Hashimoto's thyroiditis. Providers should be vigilant about the coexistence of these phenomena. We might postulate the so-called total thyroidectomy for cases with a cytologic diagnosis of Hashimoto's thyroiditis with a papillary thyroid carcinoma. As a matter of fact, this issue merits further investigation.

Background: Active surveillance has been an option for patients with low-risk papillary thyroid carcinoma (PTC). However, whether delayed surgery leads to an increased risk of local tumor metastasis remain unclear. We sought to investigate the impact of observation time on central lymph node metastasis (CLNM) and multifocal disease in patients with low-risk PTC., Methods: Patients who were diagnosed with asymptomatic low-risk PTC, and with a pathological maximum tumor size ≤1.5 cm by were included. The patients were classified into observation group and immediate surgery group, and subgroup analyses were conducted by observation time period. The prevalence of CLNM, lymph node (LN) involved >5, multifocal PTC and bilateral multifocal PTC were considered as outcome variables. The changing trend and risk ratio of prevalence over observation time were evaluated by Mann-Kendall trend test and Logistics regression., Results: Overall, 3,427 and 1,860 patients were classified to the observation group and immediate surgery group, respectively. Trend tests showed that decreasing trends both on the prevalence of CLNM and LN involved >5 over the observation time, but the difference was not statistically significant, and the prevalence of multifocal PTC and bilateral multifocal PTC showed the significant decreasing trends. After adjustment, multivariate analysis showed no statistically significant difference between observed and immediate surgery groups in the four outcome variables., Conclusion: In patients with subclinical asymptomatic low-risk PTC, observation did not result in an increased incidence of local metastatic disease, nor did the increased surgery extent in patients with delayed surgery compared to immediate surgery. These findings can strengthen the confidence in the active surveillance management for both doctors and patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Dong, Zhao, Su, Zhang, Ma, Diao, Qian, Cheng and Liu.)

Purpose: To assess tumor growth using tumor doubling rate (TDR) during active surveillance (AS) in China., Methods: Between January 2016 and June 2020, a total of 219 patients with low-risk papillary thyroid microcarcinoma (PTMC) (aged 23-75 years) were consecutively enrolled in the AS program., Results: Four sections of TDR, >0.5, 0.1~0.5, -0.1~0.1 and <-0.1, corresponded with four categories of tumor volume kinetics: rapid growth, slow growth, stable, and decreased size. We found that 10.5% of PTMCs exhibited rapid growth, 33.33% exhibited slow growth, 26.48% were stable, and 29.68% decreased in size. Tumor growth was associated with two factors: age and volume of PTMC at diagnosis. 85.72% of elderly patients (≥ 61 years old) had tumors that remained stable or even shrank and rapidly growing tumors were not found in them. When the volume was small (≤14.13 mm 3 ), the proportion of rapid growth was high (41.67%), whereas when the volume was large (> 179.5 mm 3 ), the proportion of non-growth was 68.75%., Conclusion: TDR may be a better metric for evaluating tumor growth in observational PTMCs. A certain proportion of PTMCs grow during the period of AS and tumor growth was associated with age and volume of PTMC at initial diagnosis. Therefore, how to block tumor growth during the AS period, especially for young patients and patients with early-stage PTMC (size ≤ 5 mm), will be a new challenge., Competing Interests: Author JZ was employed by Hangzhou KuaikuaiKangfu Technology Co., LTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Le, Jin, Zhong, Huang, Zhou, Zhou and Xie.)

Objectives: Thyroid cancer incidence increased over 200% from 1992 to 2018, whereas mortality rates had not increased proportionately. The increased incidence has been attributed primarily to the detection of subclinical disease, raising important questions related to thyroid cancer control. We developed the Papillary Thyroid Carcinoma Microsimulation model (PATCAM) to answer them, including the impact of overdiagnosis on thyroid cancer incidence., Methods: PATCAM simulates individuals from age 15 until death in birth cohorts starting from 1975 using 4 inter-related components, including natural history, detection, post-diagnosis, and other-cause mortality. PATCAM was built using high-quality data and calibrated against observed age-, sex-, and stage-specific incidence in the United States as reported by the Surveillance, Epidemiology, and End Results database. PATCAM was validated against US thyroid cancer mortality and 3 active surveillance studies, including the largest and longest running thyroid cancer active surveillance cohort in the world (from Japan) and 2 from the United States., Results: PATCAM successfully replicated age- and stage-specific papillary thyroid cancers (PTC) incidence and mean tumor size at diagnosis and PTC mortality in the United States between 1975 and 2015. PATCAM accurately predicted the proportion of tumors that grew more than 3 mm and 5 mm in 5 years and 10 years, aligning with the 95% confidence intervals of the reported rates from active surveillance studies in most cases., Conclusions: PATCAM successfully reproduced observed US thyroid cancer incidence and mortality over time and was externally validated. PATCAM can be used to identify factors that influence the detection of subclinical PTCs., Competing Interests: Author Disclosures Links to the disclosure forms provided by the authors are available here., (Copyright © 2024. Published by Elsevier Inc.)

Background: Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC in patients with both diseases concomitantly has been found to be more indolent than conventional PTC. Additionally, it has been well proven that BRAF mutation results in an aggressive course of PTC. The aims of this meta-analysis were to identify prevalence of BRAF mutation and its impact on clinicopathological features in patients with concomitant PTC-HT., Methods: Medline, Cochrane Library, Scopus, and Web of Science were searched until 16.09.2022, resulting in 227 articles, of which nine studies were included. Summary estimates, comparing patients with (A) BRAF (+) PTC-HT versus BRAF (+) PTC, and (B) BRAF (+) PTC-HT versus BRAF (-) PTC-HT, were generated with Review Manager 5.0., Results: In total, 6395 patients were included in this review. PTC-HT patients had significantly less BRAF mutation than PTC patients (Odds Ratio (OR) (95% Confidence Interval (CI))=0.45 (0.35-0.58), P<0.001). BRAF (+) PTC-HT patients were significantly more likely to have multifocal lesions (OR (95% CI)=1.22 (1.04-1.44), P=0.01) but less likely to have lymph node metastasis (OR (95% CI)=0.65 (0.46-0.91), P=0.01) and extrathyroidal extension (OR (95% CI)=0.55 (0.32-0.96), P=0.03) compared to BRAF (+) PTC patients. BRAF (+) PTC-HT patients were more likely to have multifocal lesions (OR (95% CI)=0.71 (0.53-0.95), P=0.02), lymph node metastasis (OR (95% CI)=0.59 (0.44-0.78), P<0.001) and extrathyroidal extension (OR (95% CI)=0.72 (0.56-0.92), P=0.01) compared to BRAF (-) PTC-HT patients., Conclusion: This meta-analysis highlights that the lower prevalence of BRAF mutation in patients with PTC-HT than conventional PTC may explain the indolent clinicopathological course in this cohort., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Janicki, Patel, Jendrzejewski and Hellmann.)

Purpose: The association between papillary thyroid cancer (PTC) and Hashimoto's thyroiditis (HT) remains a matter of debate. Several genetic and environmental factors have been found to influence this association. Because of the variation in these factors among different populations, we conducted a country- and region-based meta-analysis to examine whether the geographic area influences this association., Methods: We searched PubMed and Web of Science databases for original articles that investigated the association between HT and PTC from February 1955 to February 28, 2023. The included studies were stratified according to their country and region of origin. Various subgroup analyses were conducted. The primary outcome was the pooled relative risk (RR) and its 95% confidence interval (CI) for each region and country., Results: Forty-six studies including a total of 93,970 participants met our inclusion criteria. They originated from 16 countries distributed in five regions. Significant variation was found among countries but not among regions. Upon analysis of all 46 included studies, countries were classified based on their RR and its 95% CI. Excluding countries with pooled sample sizes <500, Sri Lanka (RR 4.23, 95% CI 2.91-6.14), Poland (RR 3.16, 95% CI 2.79-3.57) and Japan (2.68, 2.14-3.36) showed the strongest association between HT and PTC while Greece (RR 1.06, 95% CI 1.00-1.13), Spain (RR 0.70, 95% CI 0.23-2.11), and Jordan (0.62, 0.32-1.32) showed no significant association., Conclusion: Our findings revealed a variation in the association between HT and PTC among countries but not among regions. The country-to-country variation could be due to certain genetic and/or environmental factors subject to geographic variation that influence this association. These findings may help guide health policies aiming to mitigate the risk of PTC in the HT population by helping identify high-risk and low-risk countries., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: This study aimed to examine the incidence of incidental papillary microcarcinoma (PMC) and papillary thyroid carcinoma (PTC) in patients with benign multinodular goiter (MNG) and to compare their relationship with some prognostic factors from a new perspective., Methods: Bilateral total thyroidectomy (BTT) was used to evaluate the data of 716 patients who underwent a surgery for MNG. The prognostic data for these tumors and the relationship between patients with bilateral and multifocal tumors were evaluated using statistical tests., Results: Papillary carcinomas were detected in 201 patients, PMC in 134 of them, and PTCs in 67. Bilaterality was more common in patients with PTCs than in those with PMC. The incidence of bilaterality in male patients with PTC was statistically more common. The presence of intra-tumoral lymphocytes was higher in multifocal PTC cases than in unifocal PTC cases., Conclusion: The results revealed that the number of PMC s was high in incidental tumors, and patients with PTC with male sex, bilaterality, multifocality, and tumor capsule invasion were associated with poor prognosis., Competing Interests: The author(s) declare(s) that they have no conflicts of interest., (Copyright © 2023 Cigdem D. Arican et al.)

Context: It is not known how underlying subclinical papillary thyroid cancer (PTC) differs by age. This meta-analysis of autopsy studies investigates how subclinical PTC prevalence changes over the lifetime., Methods: We searched PubMed, Embase, and Web of Science databases from inception to May 2021 for studies that reported the prevalence of PTC found at autopsy. Two investigators extracted the number of subclinical PTCs detected in selected age groups and extent of examination. A quality assessment tool was used to assess bias. Logistic regression models with random intercepts were used to pool the age-specific subclinical PTC prevalence estimates., Results: Of 1773 studies screened, 16 studies with age-specific data met the inclusion criteria (n = 6286 autopsies). The pooled subclinical PTC prevalence was 12.9% (95% CI 7.8-16.8) in whole gland and 4.6% (2.5- 6.6) in partial gland examination. Age-specific prevalence estimates were ≤40 years, 11.5% (6.8-16.1); 41-60 years, 12.1% (7.6-16.5); 61-80 years, 12.7% (8-17.5); and 81+ years, 13.4% (7.9-18.9). Sex did not affect age-specific prevalence and there was no difference in prevalence between men and women in any age group. In the regression model, the OR of prevalence increasing by age group was 1.06 (0.92-1.2, P = .37)., Conclusion: This meta-analysis shows the prevalence of subclinical PTC is stable across the lifespan. There is not a higher subclinical PTC prevalence in middle age, in contrast to higher observed incidence rates in this age group. These findings offer unique insights into the prevalence of subclinical PTC and its relationship to age., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Older age is recognized as a predictor of poor prognosis in papillary thyroid carcinoma (PTC) patients. However, young age is associated with disease progression of PTC measuring 1 cm or smaller in patients on active surveillance. In this study, we investigated the relationship between patient age and prognosis of PTC belonging to very low-, low-, and intermediate-risk groups based on the guidelines published by the Japan Association of Endocrine Surgery in 2018. We enrolled 4,870 PTC patients with no high-risk features and assigned each to one of three categories: very low risk (N = 1,161), low risk (N = 1,746), and intermediate risk (N = 1,963). In very low-risk patients, the local recurrence-free survival (RFS) rate of young patients (<55 years) was significantly worse (p = 0.0437) than that of older patients (≥55 years). In low-risk patients, although age did not affect local recurrence, older patients were more likely to show distant recurrence on univariate (p = 0.0005) and multivariate analyses (p = 0.0017). In the intermediate-risk series, the local RFS rate of older patients tended to be poor (p = 0.0538), and older age was significantly associated with distant RFS (univariate, p = 0.0356; multivariate, p = 0.0439) and carcinoma death (univariate, p < 0.0001; multivariate, not done because of no other suitable factors). The prognostic significance of patient age depends on risk classification: younger age significantly predicts local recurrence in very low-risk PTC, while older age predicts worse prognosis in low- and intermediate-risk patients. These findings indicate that young age is related to rapid growth in early-phase PTC.

Context: The 2015 American Thyroid Association guidelines proposed thyroid lobectomy as an acceptable option for 1- to 4-cm papillary thyroid cancers (PTC) without extrathyroidal extension (ETE) or lymph node (LN) metastasis. However, high-risk features are often detected postoperatively, even in tumors that are considered low risk on preoperative workup. A continued evaluation is necessary to determine the optimal treatment strategies., Objective: We examined the frequency of preoperatively and postoperatively detected high-risk features in 2- to 4-cm PTCs to assess the appropriate surgical extent., Methods: All patients who underwent a thyroid surgery between 2015 and 2020 with a final diagnosis of 2- to 4-cm PTC were selected. Demographics, preoperative findings, perioperative course, and surgical pathology were retrospectively analyzed., Results: Of the entire study cohort (N = 424), 244 (57.5%) patients had at least 1 of the following high-risk features: gross ETE (18.6%), distant metastasis (1.2%), >3 LN involvement with extranodal extension (24.8%), any LN > 3 cm (0.5%), positive margin (13.2%), TERT mutation (2.6%), vascular invasion (10.8%), cN1 disease (28.5%), and > 5 LN involvement (30.4%). Two hundred patients had neither ETE nor LN metastasis on preoperative imaging, but 62/200 (31.0%) were found to have at least 1 of the aforementioned high-risk features on final pathology. Preoperative imaging had sensitivities of 75.9% and 44.4% for detecting gross ETE and LN metastasis, respectively., Conclusion: A significant portion of patients with 2- to 4-cm PTCs, including those who preoperatively met the criteria for lobectomy, were found to have high-risk features on final pathology. Careful patient selection and appropriate counseling are necessary when considering lobectomy for tumors greater than 2 cm., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: This study aimed to report the rate of thyroid malignancy in benign fine-needle aspirations (Bethesda II) at King Abdulaziz Medical City and evaluate the factors that affect false-negative outcomes of FNA., Methods: All patients referred for thyroidectomy from 2009 to 2019 were reviewed (n = 1968). Only patients with a benign FNA, corresponding to the Bethesda II, were included (n = 384). Information on age, gender, body mass index (BMI), serum thyroid-stimulating hormone, type of surgery and histopathological outcomes were retrieved., Results: Of the sample (n = 384) with an initial benign FNA, 63 patients had a malignancy on postoperative pathological examination, yielding an overall false-negative rate of 16.4%. The most frequently reported histopathological type was papillary thyroid microcarcinomas (n = 52). For the false-negative group, the mean age was 43.8 years (range 21-70 years) with an 84.1% female predominance. The surgical choice for 74% (n = 46) of cases was total thyroidectomy. Age, gender, thyroid function and BMI did not affect the false-negative rate of benign FNA (p > 0.05)., Conclusions: This study found a higher risk of malignancy compared to the literature related to benign FNA. The risk of malignancy should be considered, even with benign FNA., (Copyright © 2022 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Objective: Active surveillance (AS) has been shown to be a safe approach that can effectively block transition from overdiagnosis to overtreatment in patients with low-risk papillary thyroid microcarcinoma (PTMC). This study aimed to determine whether the AS approach can be implemented in China and investigate the population characteristics of Chinese patients who underwent AS., Methods: The epidemiologic and clinical characteristics as well as patient adherence were evaluated in 115 patients who underwent AS management as an alternative to immediate surgery for low-risk (or highly suspected) PTMC., Results: The mean patient age was 41.8 ± 10.3 years, with 41.7% and 4.4% of the patients aged <40 and ≥60 years, respectively. The median baseline diameter of index tumors was 4 (range, 3-6) mm, with 73.0% of the tumors being ≤5 mm. A total of 84.4% of the patients had a junior college, college, or graduate degree, and 83.5% were employed by the government, public institutions, companies, or technical posts. After a median 25-month follow-up, a tumor growth of ≥3 mm occurred in 3 patients (2.6%), and no new lymph node metastasis occurred. Surgery was performed in 4 patients because of patient preferences rather than because of disease progression. There was satisfactory adherence in 109 patients (94.8%) in a simulated ideal medical environment., Conclusion: The AS approach can be used as an alternative to low-risk PTMC management in China. Given the difference in epidemiologic and clinical characteristics, Chinese institutions should fully consider the features of the Chinese population while developing candidate criteria, surveillance intervals, and follow-up strategies for AS., (Copyright © 2022 AACE. Published by Elsevier Inc. All rights reserved.)

Background: It is unclear whether patients with intraductal papillary mucinous neoplasia harbor a higher risk of developing extrapancreatic malignancies., Aims: We performed a pooled estimate of the incidence of extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasia, with a particular focus on the comparison to the general population., Methods: Computerized bibliographic search of main databases was performed through February 2021. The primary endpoint was the pooled incidence of extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasms. Additional outcome was the comparison between intraductal papillary mucinous neoplasia patients and the general population, expressed in terms of standardized incidence ratio along with 95% confidence intervals., Results: Eighteen studies with 8709 patients were included. The pooled rate of metachronous extrapancreatic malignancies was 10 (6-13)/1000 persons-year. No difference was observed according to intraductal papillary mucinous neoplasia histology and sex, whereas a significantly superior incidence of extrapancreatic malignancies was observed in patients with main-duct (36.7%, 25.4%-48%) as compared to branch-duct intraductal papillary mucinous neoplasia (26.2%, 17.6%-34.8%; p = 0.03). Pooled standardized incidence ratio comparing expected rates in the general population was 1.01 (0.79-1.29); no difference was observed concerning rates of metachronous gastric cancer (standardized incidence ratio 1.60, 0.72-3.54) and colorectal cancer (1.29, 0.92-1.18), whereas biliary cancer was observed more frequently in intraductal papillary mucinous neoplasia patients (2.29, 1.07-4.93)., Conclusion: Patients with intraductal papillary mucinous neoplasia harbor an overall rate of extrapancreatic malignancies as high as 27.3%. The rate of metachronous extrapancreatic malignancies is not superior to the general population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Papillary thyroid carcinoma is the most common type of thyroid malignancy both in adults and pediatric population. Since the 1980s, there are changes in criteria in labelling thyroid lesions as "papillary thyroid carcinomas." Radiation exposure is a well-established risk factor for papillary thyroid carcinoma. Other environmental risk factors include dietary iodine, obesity, hormones, and environmental pollutants. Papillary thyroid carcinomas could occur in familial settings, and 5% of these familial cases have well-studied driver germline mutations. In sporadic papillary thyroid carcinoma, BRAF mutation is common and is associated with clinicopathologic and prognostic markers. The mutation could aid in the clinical diagnosis of papillary thyroid carcinoma. Globally, thyroid cancer is among the top ten commonest cancer in females. In both adult and pediatric populations, there are variations of prevalence of thyroid cancer and rising incidence rates of thyroid cancer worldwide. The increase of thyroid cancer incidence was almost entirely due to the increase of papillary thyroid carcinoma. The reasons behind the increase are complex, multifactorial, and incompletely understood. The most obvious reasons are increased use of diagnostic entities, change in classification of thyroid neoplasms, as well as factors such as obesity, environmental risk factors, and radiation. The prognosis of the patients with papillary thyroid carcinoma is generally good after treatment. Nevertheless, cancer recurrence and comorbidity of second primary cancer may occur, and it is important to have awareness of the clinical, pathological, and molecular parameters of papillary thyroid carcinoma., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (Copyright © 2021. Published by Elsevier Masson SAS.)

Objective: This study evaluated the impact of chronic lymphocytic thyroiditis (CLT) on clinicopathologic parameters, prognostic outcome, and initial treatment responses in patients with papillary thyroid cancer (PTC)., Methods: A retrospective review was conducted of 1409 patients with PTC, comprising 443 patients with pathology-proven PTC with CLT and 447 patients with PTC without CLT., Results: The median follow-up time was 58 months (range, 8-380 months), and the median age at the time of diagnosis was 43 years. The age at diagnosis was significantly lower in patients with CLT than in those without CLT (42 years vs 45 years, respectively; P = .001). The preoperative thyroid-stimulating hormone level was found to be significantly higher in patients with CLT than in those without CLT (1.71 mIU/L vs 1.28 mIU/L, respectively; P < .001). Multifocality and capsular, lymphovascular, and perineural invasion were detected at a higher rate in the group with CLT than in the group without CLT (P = .015, P = .024, P = .004, and P = .039, respectively). No difference was found between the 2 groups in terms of tumor size, bilaterality, extrathyroidal invasion, lymph node metastasis, disease stage, or response to treatment (P > .05)., Conclusion: The results of the present study demonstrated that the coexistence of PTC and CLT is very frequent. Patients with the coexistence of PTC and CLT were diagnosed at a younger age, and the thyroid-stimulating hormone level was higher in these patients. Contrary to previous studies, no positive effect of the CLT and PTC combination was detected on any clinicopathologic factor. In addition, lymphovascular and perineural invasions, which had negative effects on prognosis, were more common in the group with CLT., (Copyright © 2021 AACE. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the relationship between triglyceride (TG) levels and aggressive pathological characteristics in papillary thyroid microcarcinoma (PTMC) patients, especially the relationship between TG, BMI, age, and extrathyroidal extension (ETE)., Methods: A retrospective analysis of 9663 patients with PTMC in a single center from 2010 to 2017 was included in this study. Binary logistic regression was used to analyze the relationship between serum TG and aggressive pathological characteristics of PTMC in different genders. Further analyzing the risk of high TG in different ages and BMI groups., Results: Even after adjustment for confounding factors, high TG is still a risk factor for ETE in women with PTMC, but not a risk factor for men. Compared with the group with lower than 0.90 mmol/L, when the TG level is higher than 1.93 mmol/L, the risk of ETE in women increased by about 1.35-fold. The remaining two variables (BMI, age) as risk factors for ETE are analyzed. In the normal BMI group, high TG is still a risk factor for ETE. The risk of ETE in women more than 55 years old is significantly increased by 1.96-fold (1.34-fold in less than 55 years)., Conclusion: High TG in women is positively correlated with the risk of ETE in PTMC. PTMC with high TG in elderly women (more than 55 years) has a higher risk of ETE. TG is a potential serological index for predicting the risk of ETE in women with normal BMI., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Papillary thyroid microcarcinoma is defined as papillary thyroid cancer with a diameter of ≤1 cm. Despite its prevalence, there is wide variation in practice in the investigation and management of patients with papillary thyroid microcarcinoma throughout the UK and internationally. The primary aim of this paper is to describe the experience of investigation and management in a Scottish health board over the past 10 years., Methods and Results: Retrospective analysis of thyroidectomy and hemithyroidectomy resection samples from March 2009 to March 2020. 532 specimens were reviewed and 20 patients with PTMC were identified. 12 patients had an incidental finding of PTMC. Median U score- 3, Median Thy score- 2.5 for dominant or radiologically suspicious nodules. 8 specimens demonstrated aggressive histopathological features. 1 patient with positive nodal disease in the neck and 0 patients with positive nodal disease in the thorax on CT Neck and Chest., Conclusion: Here we report the first UK Cohort describing the radiological investigation and management of papillary thyroid microcarcinoma. The results of our study are in accordance with a recent meta-analysis which found 4% nodal disease and 0.025% distant metastasis at time of presentation in patients with PTMC.

Background: Recalibrating diagnostic thresholds or using alternative labels may mitigate overdiagnosis and overtreatment of papillary microcarcinoma (mPTC). We aimed at identifying and collating relevant epidemiological evidence on mPTC, to assess the case for recalibration and/or new labels. Methods: We searched EMBASE and PubMed databases from inception to December 2020 for natural history, autopsy, diagnostic drift, and diagnostic reproducibility studies. Where a relevant systematic review was pre-identified, only new articles were additionally included. Non-English articles were excluded. One author screened titles and abstracts. Two authors screened full text articles, performed quality assessments, and extracted data. We undertook narrative synthesis of included evidence (pooled estimates from systematic reviews and single estimates from primary studies). Results: One systematic review of patients undergoing active surveillance found that after 5 years of follow-up, 5.3% (95% confidence interval [CI 4.4-6.4%]) of the mPTC lesions had increased in size by ≥3 mm, and 1.6% [CI 1.1-2.4%] of patients had lymph node metastases. Among 7 new primary studies (including 3 updates on 2 studies included in the systematic review), 1-5% of patients undergoing active surveillance had lymph node metastases after a median follow-up of 1-10 years. One systematic review found that subclinical thyroid cancer incidentally discovered at autopsy is relatively common, with a pooled prevalence of 11.2% [CI 6.7-16.1%] among studies that examined the whole thyroid. Four diagnostic drift studies evaluated the new classification of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Three studies of cases previously diagnosed as papillary thyroid cancer found 1.3-2.3% were reclassified as NIFTP (reclassifications were from follicular variation of papillary thyroid cancer [FVPTC]). One study of 48 cases previously diagnosed as mPTC found that 23.5% were reclassified as NIFTP. Thirteen reproducibility studies of papillary thyroid lesions found substantial variation in the histopathological diagnosis of thyroid lesions, including FVPTC and NIFTP classifications (no study evaluated mPTC). Conclusions: This review supports consideration of recalibrating diagnostic thresholds and/or alternative labels for low-risk mPTC.

Background: The management of papillary thyroid microcarcinomas with TERT ± BRAF V600E mutations remains controversial owing to their potential associations with tumor aggressiveness. This study evaluated the clinical implications of these mutations in management of patients with papillary thyroid microcarcinomas., Methods: Between June 2019 and October 2020, surgical specimens from 504 consecutive patients with papillary thyroid microcarcinomas were obtained at a tertiary hospital. The mutation statuses of TERT promoter and BRAF V600E were assessed by polymerase chain reaction. The prevalence and relationships of TERT ± BRAF V600E mutations with clinical, radiological, and pathological characteristics were evaluated., Results: Of 504 patients with papillary thyroid microcarcinomas, TERT ± BRAF V600E mutations were found in 3.2% (16/504). Of these 16 patients, 93.8% (15/16) of papillary thyroid microcarcinomas with TERT promoter mutations also harbored BRAF V600E mutations. Correlation analysis showed that TERT ± BRAF V600E mutations were not associated with aggressive clinical, radiological, or pathological features (P > .05). The presence of lymph node metastasis was not associated with mutation status (P = .834)., Conclusion: TERT ± BRAF V600E mutations in patients with papillary thyroid microcarcinomas are not associated with any unfavorable clinicopathological features, including lymph node metastasis status., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: there is a dearth of data on the epidemiology of breast tumors in the Kingdom of Saudi Arabia (KSA). This study aimed to determine the demographics, clinical patterns, and their association with histopathological types of breast tumors among females presently residing in KSA., Methods: a multi-centric, cross-sectional study including female patients with symptoms suggestive of breast tumor was conducted at three hospitals in KSA from February 2019 to February 2020. The patient´s electronic health records were used to collect information related to their demographics, clinical findings including comordbities and symptoms and investigations. Binary logistic regression models were used to determine factors associated with the breast tumors., Results: a total of 270 female patients were included in the study. The most frequently encountered symptom was a breast lump (95.9%, n = 259), followed by pain (18.9%, n = 51). More than half the population (53%, n = 143) had a histopathological diagnosis of fibroadenoma. Multivariate analysis revealed that patients > 46 years of age were less likely to present with fibroadenoma (AOR: 0.049 95% CI 0.02 - 0.15; p < 0.005). Those in the 31 - 45 years age group were less likely to present with ductal/lobular/papillary carcinomacompared to the less than 30 years group (AOR: 0.42, 95% CI 0.18 - 0.97; p = 0.04)., Conclusion: in this population of Saudi women with symptoms suggestive of breast tumor, those aged less than 40 years were more likely to have a fibroadenoma whereas those above 40 years were more likely to have breast cancer., Competing Interests: The authors declare no competing interests., (Copyright: Mohamed Abdel Razik et al.)

Introduction: thyroid cancer (TC) is considered to have become the fastest growing cancer in terms of incidence worldwide. Despite literature reporting a prevalence of 5-10% in clinically identified thyroid nodules, Cameroon still has limited data on the profile of TCs in patients with Nodular Goitres (NGs). The Objective were to describe the epidemiological, diagnostic and therapeutic profiles of TCs in patients with nodular goitres at the Douala General Hospital (DGH)., Methods: this was a retrospective cross-sectional analysis of patient records with diagnoses of NGs, over 11 years (2006 to 2016) at the DGH., Results: overall, 187 patients (mean age= 46.8±13.9 years, men=27 (14.4%)) were included; 43 (23%) cancers were identified. The most common histological type was papillary cancer (50%). Nodule size of >4cm and hypoechogenicity were independently associated with malignancy. Most patients presented with TNM stage II (47.4%) and well-differentiated cancers were considered to be predominantly at low-risk according to MACIS (55%) and AMES (74%) scores. Surgery was offered to 95.3% of patients., Conclusion: TCs are frequent in patients with NGs with papillary cancer dominating. A high index of suspicion should be held if a nodule is >4cm and/or is hypoechogenic. Prognostic studies are needed to describe the outcome of TCs in our setting., Competing Interests: The authors declare no competing interests., (Copyright: Edgar Mandeng Ma Linwa et al.)

Objective: The hobnail variant of papillary thyroid carcinoma (HVPTC) has emerged as a rare and aggressive variant of papillary thyroid carcinoma (PTC). We aim to determine the prevalence and clinicopathologic factors of HVPTC., Methods: A systematic review of the literature for studies examining HVPTC was performed. Four databases (PubMed, Scopus, OVID, Cochrane library) were queried from inception of databases through March 20th, 2020., Results: Sixteen studies with 124 cases of HVPTC were included. The mean age for all patients was 52.3 years. HVPTC had a prevalence of 1.08% out of all PTC cases, with a mean tumor size of 3.1 cm. In 62% and 50% of cases, lymphovascular invasion and extrathyroidal extension were present, respectively. Follow-up data, with a mean of 49.9 months, revealed a 66% rate of lymph node metastasis and 23% rate of distant metastasis. Tumors with ≥30% hobnail morphology had a 2.6-fold increased odds of developing lymph node metastasis compared with <30% hobnail morphology, however did not differ in rates of distant metastasis. Patients ≥55 years old had a 4.5-fold increased odds of distant metastasis and a 4.7-fold increased odds of lymphovascular invasion over patients <55., Conclusions: High rates of locoregional and distant disease as well as high-risk pathological factors reveal the aggressive nature of HVPTC. Diagnostic criteria regarding percentage of hobnail morphology requires further refinement. Further studies are warranted in order to better understand how recognition of this high-risk variant impacts clinical treatment.

Purpose: The incidence of papillary thyroid microcarcinoma is increasing. We evaluated the recurrence-free survival following total thyroidectomy and lobectomy to identify the optimal surgical choice., Methods: A meta-analysis was performed using the National Library of Medicine and the National Institutes of Health PubMed database to identify eligible studies. Summary 5- and 10-year RFS estimates after TT versus LT were calculated using random effects models., Results: The literature search yielded 1117 studies (1990-2019). Nine studies met the inclusion criteria comprising 10,186 total thyroidectomy and 11,408 lobectomy patients. The 5-year recurrence-free survival was 98% [95% confidence interval (CI) 97-99%] after total thyroidectomy and 97% (95% CI 96-99%) after lobectomy, based on eight studies (9421 total thyroidectomy and 11,283 lobectomy patients); the 10-year recurrence-free survival was 95% (95% CI 92-98%) after total thyroidectomy and 92% (95% CI 86-96%) after lobectomy, based on eight studies (total thyroidectomy = 10,100, lobectomy = 11,389 patients)., Conclusion: The present meta-analysis demonstrates excellent, long-term recurrence-free survival following both total thyroidectomy and lobectomy surgery in patients with papillary thyroid microcarcinoma. The analysis also suggests that patients undergoing total thyroidectomy trended toward a slightly better long-term 10-year recurrence-free survival in comparison to patients undergoing lobectomy, a finding of potential, clinical significance in the management decision-making process.

Context: The long-term quality of life (QoL) in patients with low-risk papillary thyroid microcarcinoma (PTMC) underwent active surveillance (AS) and immediate surgery is unclear., Objective: The aim of this study was to investigate the effect of initial treatment choice on 2-year QoL in patients with low-risk PTMC., Design, Setting, and Participants: We analyzed 2652 QoL surveys from 1055 subjects enrolled in ongoing multicenter prospective cohort study on active surveillance of PTMC, in which the median follow-up duration was 24.4 months., Major Outcome Measure: We evaluated QoL of patients with low-risk PTMC according to their treatment modality using generalized estimating equation., Results: Six hundred and seventy-four subjects (male = 161; mean age = 48.8 ± 11.9 years) with low-risk PTMC chose AS while 381 subjects (male = 75; mean age = 45.7 ± 10.4 years) chose immediate surgery, including lobectomy/isthmusectomy (L/I) and total thyroidectomy (TT). Among the 817 subjects who completed baseline QoL surveys, 2-year QoL was good in order of AS (n = 500), L/I (n = 238), and TT (n = 79) groups after adjustment for age, sex, baseline tumor size, and baseline QoL scores. Among the 101 subjects who changed their treatment from AS to surgery during the follow-up period, 35 subjects who changed treatment due to disease progression had better QoL than 66 subjects who had no disease progression., Conclusions: This study identified QoL as a major issue in choosing an initial treatment of low-risk PTMC and highlighted the possibility of using AS as the primary treatment., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Rates of thyroid cancer in patients with multinodular goitre (MNG) vary widely, from 3 per cent in older studies to 35 per cent in more recent studies. The purpose of the present study was to evaluate the prevalence of thyroid cancer in patients operated on for MNG, and to determine risk factors for incidental thyroid malignancy., Methods: A prospectively developed database of all patients who underwent thyroidectomy for a benign MNG at the high-volume endocrine surgery unit of a tertiary referral university hospital was interrogated., Results: A total of 3233 patients were analysed, separated into three groups according to their functional thyroid status (hypothyroid, hyperthyroid or euthyroid). There were 2788 women (86.2 per cent); the mean patient age was 56.4 years and mean preoperative disease duration was 106.2 months. Incidental thyroid cancer was identified in 1026 patients (31.7 per cent), of which 917 (89.4 per cent) were papillary cancers. Multivariable regression analysis identified functional thyroid status, younger age, male sex, smaller adenoma size, smaller thyroid glands, Hashimoto's thyroiditis and chronic non-specific thyroiditis as independent risk factors for thyroid cancer., Conclusion: MNG was associated with a considerable rate of incidental thyroid cancer, which has been underestimated. A variety of factors should be taken into account when considering the malignant potential of a presumed benign MNG., (© The Author(s) 2020. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: Bilateral papillary thyroid carcinoma (PTC) requires aggressive treatment, such as total thyroidectomy (TT). If there is only an isolated PTC focus in one lobe that can be diagnosed preoperatively, and it is unknown whether there are foci in the contralateral lobe that are too small to be detected, it is difficult to know whether to perform TT or to remove only the lobe with the isolated PTC focus. Here, we investigated the prevalence of and predictive factors for occult bilateral PTC that was only diagnosed unilaterally before surgery., Methods: This retrospective study involved 586 patients with unilateral PTC who were diagnosed preoperatively by ultrasound. They underwent TT and cervical lymph node dissection. According to the pathology, they were divided into unilateral PTC and bilateral (Bil)-PTC groups. Student's t test, chi-squared test, and multivariate analysis were performed to identify features of the malignant tumor that increased the likelihood of malignancy in the contralateral lobe. The prevalence of occult Bil-PTC was calculated., Results: Bil-PTC was found in 70 of 586 (11.95%) PTC patients. Multivariate analysis showed that vascularity (odds ratio[OR]: 2.180, 95% confidence interval [CI]: 1.142-4.162, p = 0.018) and ultrasound diagnosis of lymph node metastasis (USLNM) (OR: 2.056, 95% CI: 1.056-4.004, p = 0.034) were independent predictors of occult Bil-PTC., Conclusion: The prevalence of occult PTC in the contralateral lobe was only 11.95%. Vascularity and USLNM were risk factors for Bil-PTC. In terms of these preoperative risk factors for PTC, TT should be cautiously performed in patients with preoperative diagnosis of PTC with isolated focus., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Although the incidence of papillary thyroid microcarcinoma (PTMC) has increased in recent decades, the role played by minimal extrathyroidal extension (mETE) in the prognosis of PTMC is still unclear. The aim of this study is to analyze the factors associated with PTMC with mETE and its long-term prognosis., Material and Methods: We conducted a retrospective study on patients with a histological diagnosis of PTMC. We excluded patients who had previously undergone thyroid surgery, those who had other synchronous malignancies, those with an ectopic location of the PTMC, and those lost to follow-up within two years. We compared group 1 (PTMC without extrathyroidal extension) to group 2 (PTMC with mETE) and performed a multivariate analysis., Results: We observed PTMC with mETE in 11.2% (n = 18) of patients. On the multivariate analysis, mETE was associated with an age ≥45 years (OR: 4.383; 95% CI: 1.051-18.283, p = .043), tumor size ≥8 mm (OR: 5.913; 95% CI: 1.795-19.481; p = .003), bilaterality (OR: 4.430; 95% CI: 1.294-15.173; p = .018) and metastatic lymph nodes (OR: 12.588; 95% CI: 2.919-54.280; p = .001). Over the mean follow-up period of 119.8 ± 65 months, one case of recurrence was detected in group 2 (0% vs. 5.6%; p = .112). No patients died of the disease. Disease-free survival was lower in group 2 (124.9 ± 5.6 vs. 97.4 ± 10.3 months; p = .034)., Conclusions: The mETE of PTMC is a factor of worse prognosis associated with the presence of metastatic lymph nodes and a lower rate of disease-free survival., (Copyright © 2020 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Objective: To conduct a systematic review and meta-analysis to estimate the prevalence of occult uterine malignancy of any subtype specifically at the time of hysterectomy for pelvic organ prolapse (POP)., Methods: We primarily used MEDLINE to access existing literature. The search terms used were "occult malignancy" or "occult uterine pathology" paired with "morcellation" or "hysterectomy." Our cutoff date for articles was March 25, 2019. We further narrowed articles down based on whether they included data on occult malignancy at time of hysterectomy specifically for POP., Results: Our search yielded a total of 233 journal articles, of which 53 met the criteria for a full-text review. Eight studies provided specific data on occult uterine malignancy among women undergoing surgery for POP and formed the basis for this meta-analysis. Among the 8 studies examined, the total number of patients combined was 35,880, and there were 144 total occult uterine malignancies. There were 7 case series and 1 population-based study included. The pooled prevalence of occult uterine malignancy at the time of hysterectomy for POP was 0.22% (95% confidence interval, 0.11%-0.35%]. There was very little heterogeneity observed across the 8 studies (I2 = 12.06%, Q χ2[7] = 7.96, P = 0.336)., Conclusions: The pooled prevalence of occult uterine malignancy, of any subtype, at the time of surgery for POP specifically is 0.22% based on meta-analysis of existing studies. Surgeons can use this statistic as part of the preoperative counseling of patients with POP before hysterectomy., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2020 American Urogynecologic Society. All rights reserved.)

Background: In contrast to the rapid increase in thyroid cancer incidence, the mortality has remained low and stable over the last decades. In Ecuador, however, thyroid cancer mortality has increased. The objective of this study is to determine possible drivers of high rates of thyroid cancer mortality, through a cross-sectional analysis of all patients attending a thyroid cancer referral center in Ecuador., Methods: From June 2014 to December 2017, a cross-sectional study was conducted at the Hospital de Especialidades Eugenio Espejo, a regional reference public hospital for endocrine neoplasia in adults in Quito, Ecuador. We identified the mechanism of detection, histopathology and treatment modalities from a patient interview and review of clinical records., Results: Among 452 patients, 74.8% were young adults and 94.2% (426) were female. 13.7% had a family history of thyroid cancer, and patients' median tumor size was 2 cm. The incidental finding was 54.2% whereas 45.8% was non-incidental. Thyroid cancer histology reported that 93.3% had papillary thyroid cancer (PTC), 2.7% follicular, 1.5% Hurtle cells, 1.6% medullary, 0.7% poor differentiated, and 0.2% anaplastic carcinoma. The mean MACIS (metastasis, age, completeness, invasion, and size) score was 4.95 (CI 4.15-5.95) with 76.2% of the thyroid cancer patients having MACIS score less than or equal to 6. The very low and low risk of recurrence was 18.1% (79) and 62% (271) respectively. An analysis of 319 patients with non-metastatic thyroid cancer showed that 10.7% (34) of patients had surgical complications. Moreover, around 62.5% (80 from 128 patients with thyroglobulin laboratory results) of TC patients had a stimulated-thyroglobulin value equal or higher than 2 ng/ml. Overall, a poor surgical outcome was present in 35.1% (112) patients. Out of 436 patients with differentiated thyroid carcinoma, 86% (375) received radioactive iodine., Conclusion: Thyroid cancer histological characteristics and method of diagnosis are like those described in other reports without any evidence of the high frequency of aggressive thyroid cancer histology. However, we observed evidence of overtreatment and poor surgical outcomes that demand additional studies to understand their association with thyroid cancer mortality in Ecuador.

At present, mostly case-control and retrospective studies have investigated the association between etiologic risk factors and the development of histologic subtypes of renal cell carcinoma (RCC). Therefore, we assessed the heterogeneity between body mass index (BMI), cigarette smoking, alcohol consumption and hypertension across clear-cell RCC (ccRCC) and papillary RCC (pRCC) risk in the prospective Netherlands Cohort Study on diet and cancer. In 1986, 120 852 participants aged 55 to 69 completed a self-administered questionnaire on diet and other risk factors for cancer. Participants were followed up for cancer through record linkage. Tumor histology was assessed through centralized revision by two experienced uropathologists. After 20.3 years of follow-up, 384 histologically verified RCC cases, including 315 ccRCC and 46 pRCC cases and 4144 subcohort members were eligible for case-cohort analysis. Hazard ratios and 95% confidence intervals were estimated by multivariable-adjusted proportional hazards models. Overall, BMI was associated positively with ccRCC risk, but inversely with pRCC risk. Cigarette smoking was associated with an increased ccRCC, but a decreased pRCC risk. Alcohol consumption was inversely associated with both ccRCC and pRCC risk. Hypertension was associated with an increased risk of both ccRCC and pRCC. Statistically significant etiologic heterogeneity was observed for BMI, BMI change since age 20, and smoking duration in current smokers across ccRCC and pRCC risk. In conclusion, we observed potential heterogeneity for BMI, BMI change and smoking duration across ccRCC and pRCC risk., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)

Objective: Some surgeons believe that dissection posterior to the right recurrent laryngeal nerve lymph node (PRRLN-LN) is unnecessary for the low metastasis rate and high complication risk. However, persistent metastatic lymph nodes may have a higher recurrence rate, surgical risk, and complications. Thus, it is important to distinguish patients who require PRRLN-LN dissection. To identify the risk factors for lymph nodes posterior to the right recurrent laryngeal nerve metastasis (LN-prRLN) and establish a scoring system to help determine whether PRRLN-LN dissection is required in patients with papillary thyroid carcinoma., Methods: 821 participants were randomly allocated to the development and validation cohorts in a 2:1 ratio. A nomogram-based predictive model for LN-prRLN was established based on the risk factors identified in the development cohort., Results: LN-prRLN was diagnosed pathologically in 124 of 821 patients (15.1%) from the entire cohort. Multivariate analysis identified age (odds ratio [OR], 0.964; 95% CI, 0.945-0.983; P < .001), tumor size (OR, 1.536; 95% CI, 1.135-2.079; P = .005), extrathyroidal extension (OR 2.271, 95% CI, 1.368-3.770; P = .002), clinically involved right central compartment lymph node metastasis (OR 1.643, 95% CI, 1.055-2.559; P = .028), and right lateral lymph node metastasis (OR 4.271, 95% CI, 2.325-7.844; P < .001) as the predictors of LN-prRLN. A risk model was established and well validated. Calibration curves to evaluate the nomogram in both the development and validation cohorts revealed a concordance index of 0.756 ± 0.058 and 0.745 ± 0.042, respectively., Conclusion: Our scoring system may be useful for helping the surgeons decide which patients should undergo the dissection of PRRLN-LN., (Copyright © 2020 AACE. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate whether a computer-aided diagnosis (CAD) program developed using the deep learning convolutional neural network (CNN) on neck US images can predict the BRAFV600E mutation in thyroid cancer., Methods: 469 thyroid cancers in 469 patients were included in this retrospective study. A CAD program recently developed using the deep CNN provided risks of malignancy (0-100%) as well as binary results (cancer or not). Using the CAD program, we calculated the risk of malignancy based on a US image of each thyroid nodule (CAD value). Univariate and multivariate logistic regression analyses were performed including patient demographics, the American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TIRADS) categories and risks of malignancy calculated through CAD to identify independent predictive factors for the BRAFV600E mutation in thyroid cancer. The predictive power of the CAD value and final multivariable model for the BRAFV600E mutation in thyroid cancer were measured using the area under the receiver operating characteristic (ROC) curves., Results: In this study, 380 (81%) patients were positive and 89 (19%) patients were negative for the BRAFV600E mutation. On multivariate analysis, older age (OR = 1.025, p = 0.018), smaller size (OR = 0.963, p = 0.006), and higher CAD value (OR = 1.016, p = 0.004) were significantly associated with the BRAFV600E mutation. The CAD value yielded an AUC of 0.646 (95% CI: 0.576, 0.716) for predicting the BRAFV600E mutation, while the multivariable model yielded an AUC of 0.706 (95% CI: 0.576, 0.716). The multivariable model showed significantly better performance than the CAD value alone (p = 0.004)., Conclusion: Deep learning-based CAD for thyroid US can help us predict the BRAFV600E mutation in thyroid cancer. More multi-center studies with more cases are needed to further validate our study results., Competing Interests: The authors have declared that no competing interests exist.

Purpose of Review: The purpose of this review is to describe the contemporary evaluation and management of tall cell variant of papillary thyroid carcinoma with an emphasis on the clinical features., Recent Findings: Tall cell variant of papillary thyroid carcinoma is the most common aggressive subtype. Within the last few years, the diagnostic criteria for this entity have evolved. Studies have elucidated a better understanding of the clinical implications and pathophysiology of this variant. In this review, the studies presented reflect cumulative and aggregated data from metaanalyses, systematic reviews, and large database investigations utilizing the current diagnostic criteria., Summary: Overall, tall cell variant of papillary thyroid carcinoma represents an aggressive subtype of well-differentiated thyroid carcinoma with more prevalent high-risk features and a poorer clinical outcome.

Purpose: To describe the outcomes and the incidence of adverse events following active surveillance (AS) versus immediate surgery in patients with low-risk papillary thyroid carcinoma (PTC)., Methods: We prospectively evaluated 286 patients who attended the Hospital de Clínicas, with a single thyroid nodule <1.5 cm classified as Bethesda category V or VI (PTC). Those patients with no aggressive features were considered as harboring a low-risk PTC and were offered AS or immediate surgery. For patients who opted for AS, surgery was recommended if tumor progression was observed. Post-operative adverse events were recorded for those patients treated with surgery (after AS or immediate surgery)., Results: From 286 eligible patients, 164 harbored a low-risk PTC. Among these, 75% (n = 123) underwent immediate surgery and 25% (n = 41) opted for AS. Within the last group, increase in tumor size more than 3 mm was observed in 14.6 and 4.8% was diagnosed with lymph-node metastases after a median of 37.5 months (range, 12-65) of follow-up. One hundred and thirty five patients underwent surgery: in 123, it was immediate after diagnosis and in 12 after a median of 35 months (range, 12-65) of AS. Both groups had excellent oncological outcomes. The frequency of postoperative adverse events was 24.4%, which was permanent in 9.6% of cases. The immediate-surgery group presented higher incidence of permanent vocal cord paralysis (2.4 vs. 0%); permanent hypoparathyroidism (5.7 vs. 0%) and local complications (4 vs. 2.4%) compared with the AS group, all non-statistically significant., Conclusions: The high incidence of postoperative complications observed in our media could be avoided if AS was performed as the initial approach in patients with low-risk PTCs. The frequency of tumor growth and LN metastases during AS was similar to other series.

Introduction: Papillary thyroid microcarcinoma (PTMC) is defined as a tumor with a larger diameter ≤ 1 cm and is considered having an indolent course and an excellent prognosis. Nevertheless, the incidence of lymph node metastasis in PTMC is not negligible, reaching up to 65% in some series. The aim of this study was to assess the incidence of lymph node metastasis in patients with PTMC and to evaluate predictive factors for lymph node metastasis. Methods: We included in this retrospective observational study patients who underwent thyroidectomy with pathological diagnosis of PTMC at our department from January 2003 to June 2019. Results: Two hundred ninety-three patients were included in the study. The incidence of lymph node metastasis was 13.7%. Multivariate analysis revealed as independent risk factors for lymph node metastasis age <45 years, nodule size ≥6 mm, tall cell variant of PTC, extrathyroidal extension, and angioinvasion. Conversely, autoimmune thyroiditis was found as a protective factor for lymph node metastasis. A subgroup of patients, with nodule size ≤ 5 mm, presented non-aggressive features. Conclusion: The incidence of lymph node metastasis in PTMC is considerable; the size of the tumor appears to be the most significant predictive factor for lymph node metastasis. The traditional cut-off value used for definition of microcarcinoma could be reconsidered to identify patients with an indolent course of the tumor, where active surveillance could be the appropriate treatment, and on the other hand, patients with potentially aggressive tumors requiring an adequate surgical intervention. Clinical Trial Registration: The trial was registered at ClinicalTrials.gov (ID: NCT04274829)., (Copyright © 2020 Medas, Canu, Cappellacci, Boi, Lai, Erdas and Calò.)

Objective: We examined the relationships between tumor tissue calcifications of papillary thyroid cancer (PTC), body mass index (BMI), and tumor invasiveness., Methods: This was a retrospective analysis of 13,995 patients with PTC. Comparisons were made between the clinical and pathologic features of the tumor tissue calcifications group and non-tumor tissue calcifications group. Odds ratios (ORs) of tumor tissue calcifications, BMI, and tumor invasiveness features were calculated using a binary logistic regression model. We analyzed the relationship between tumor tissue calcifications and certain characteristics of thyroid cancer based on the pathologic findings., Results: BMI was positively correlated with tumor tissue calcifications in patients with PTC (OR, 1.015; P = .011), and obesity increased the risk of tumor tissue calcifications (OR, 1.374; P = .038). Calcifications were positively correlated with T-size (OR, 1.899; P<.001), multifocality (OR, 1.217; P<.001), extrathyroidal extension (ETE) (OR, 1.287; P<.001), high T-stage (OR, 1.765; P<.001), N+ (OR, 1.763; P<.001), and a higher number of lymph node metastases (OR, 1.985; P<.001). Compared with normal-weight patients with tumor tissue calcifications, obese patients with tumor tissue calcifications had an increased risk of ETE (OR obesity , 1.765 vs. OR normal , 1.300) and N+ (OR obesity , 1.992 vs. OR normal , 1.784)., Conclusion: Tumor tissue calcifications are positively correlated with the invasiveness of PTC. Obesity further promotes the risk of tumor invasiveness in PTC combined with tumor tissue calcifications. These findings suggest that more comprehensive evaluations by trained pathologists may help physicians identify the optimal therapeutic regimens in the postoperative period., Abbreviations: BMI = body mass index; CI = confidence interval; ETE = extrathyroidal extension; FT3 = free triiodothyronine; OR = odds ratio; PTC = papillary thyroid carcinoma; RET = rearranged during transfection; TTC = tumor tissue calcification; US = ultrasonography; USC = ultrasonography calcification; WHO = World Health Organization., (© 2020 American Association of Clinical Endocrinologists. Published by Elsevier, Inc. All rights reserved.)

The anti-thyroglobulin antibody (TgAb) has been suggested to be more common in patients with papillary thyroid cancer (PTC). Here, we performed a retrospective study investigated the correlation between TgAb level and PTC in Chinese patients between 2011 and 2015. Patients with goiter who underwent thyroidectomy and received a confirmed pathological diagnosis were enrolled into the study. Clinical characteristics and preoperative thyroglobulin antibody (TgAb) level data were collected from all enrolled patients. Based on the preoperative TgAb test results, patients were divided into a TgAb negative (TgAb-) group (<60 IU/mL) and a TgAb positive (TgAb+) group (≧60 IU/mL). Of the 4,046 patients, 671 patients were TgAb+ while 3,375 patients were TgAb-. There were 535 (79.7%) patients with PTC in the TgAb+ group, and 2,154 (63.8%) patients with PTC in the TgAb- group. The prevalance of PTC was significantly higher in TgAb+ patients than in TgAb- patients. TgAb+ patients were stratified into four groups based on the TgAb titer. The prevalence of PTC did not increase with TgAb titer. No significant difference in TgAb level was noted in patients with different clinicopathologies, including TNM stage, lymph node metastasis, and multifocal carcinoma. Regression analysis suggested a higher risk of PTC malignancy among TgAb+ patients. Preoperative TgAb level ≥60 IU/mL might be associated with a higher risk of PTC. However, there was no titer-dependent association between elevated TgAb titer and PTC malignancy., (Copyright © 2020 Jia, Pang, Wang, Zhao, Jiang, Song, Fan, Wang, Zhao, Ba, Yang, Wang, Gu, Zang, Pei, Du, Mu and Lyu.)

Background: Intracystic/encapsulated papillary carcinoma remains a poorly understood disease of the breast with a little amount of reports that describe it. It shares features with DCIS and IDC and predominantly affects postmenopausal women. This study aims to evaluate the clinical presentation, treatment, and outcomes in IPC patients managed at our institution., Methods: We retrospectively pooled twenty-eight IPC patients' medical records at our institution. Descriptive analysis of clinicopathological characteristics, approach, and outcomes was done along with a quantitative statistical analysis., Results: Cases were divided into three groups: isolated IPC, IPC associated with DCIS, and IPC associated with Invasive Carcinoma. Treatment modalities varied according to the IPC type and its associated components. All patients presented with a palpable mass. Immunohistochemical staining revealed that all isolated IPCs were ER and PR positive and HER2 negative. Lymph node dissection proved necessary only in IPC associated invasive carcinoma. Irregular borders and lobulations, among others, were found on non-invasive core biopsies that turned out to be associated with invasion on surgical pathology. All patients were alive after a median follow-up time of 23 months when the study was over with no reports of recurrence., Conclusion: IPC cases and treatment approaches at our institution appear similar to the available literature and confirm the excellent prognosis among IPC. Even more, further studies into the key features such as BMI, family history, and radiological findings are necessary for a potential algorithm that could assess for risk of finding invasion in surgical pathology and subsequently the need for axillary/sentinel lymph node biopsy.