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Occult papillary carcinoma of the thyroid. A "normal" finding in Finland. A systematic autopsy study
Abstract
The thyroids from 101 consecutive autopsies from Finland were subserially sectioned at 2- to 3-mm intervals. From 36 thyroids, 52 foci of occult papillary carcinoma (OPC) were found, giving a prevalence rate of 35.6%, the highest reported rate in the world. The rate was higher, although not significantly, in males (43.3%) than in females (27.1%), but it did not correlate to the age of the patients. Twenty-six glands contained one tumor focus and ten glands contained two to five tumor foci. Only a minority of the smallest tumors can be detected with the method used. The probable number of OPCs over 0.15 mm in diameter was calculated to be about 300 in this material. The tumor diameter varied from 0.15 mm to 14.0 mm, with 67% of tumors under 1.0 mm. The smallest tumors were usually circumscribed and were composed almost solely of follicles. Larger tumors had more papillary structures and were often invasive. Fibrosis and, in the largest OPCs, lymphocytic reaction were seen around the invasive islands. All tumors were positively stained for thyroglobulin and all but one of the tumors stained positively for epidermal keratin. OPC appears to arise from follicular cells of normal follicles. Apparently the great majority of the tumors remain small and circumscribed and even from those few tumors that grow larger and become invasive OPCs only a minimal proportion will ever become a clinical carcinoma. According to the study, OPC can be regarded as a normal finding which should not be treated when incidentally found. In order to avoid unnecessary operations it is suggested that incidentally found small OPCs (less than 5 mm in diameter) were called occult papillary tumor instead of carcinoma.
... 3. Determinar la distribución por edad y género y valorar cuál de los siguientes factores de riesgo presentaba cada paciente: antecedentes personales de radioterapia de cabeza-cuello, antecedentes familiares de carcinoma diferenciado de tiroides. 4. Conocer si hay asociación entre los factores que agravan el pronóstico como: multifocalidad, invasión capsular, metástasis ganglionares al diagnóstico y los factores de riesgo para CPT. ...
... A pesar de este aumento de la incidencia, la tasa de mortalidad se ha mantenido estable, con buen pronóstico y elevada sobrevida a largo plazo. Estudios realizados en autopsias revelan ocurrencia de MCPT de 6% a 36%, según el de ITO la detección en autopsias va de 0,5% a 5,2% (4)(5)(6)(7) . ...
... Las guías actuales indican que pacientes con CPT no agresivo, unifocal, sin extensión locorregional o invasión, no necesitan ablación con RY, esta recomendación se basa en que no se ha encontrado mejoría en la morbilidad/recurrencia ni en la mortalidad en los pacientes con MCPT. Sin embargo, podría considerarse en pacientes con CPT con factores de mal pronóstico (4) . ...
Introducción:
el microcarcinoma papilar tiroideo (MCPT) es un tumor <1 cm, indolente y con diagnóstico incidental o asintomático. Su incidencia aumentó últimamente por mayor detección ecográfica de nódulos no palpables, pero la mortalidad se mantiene estable, con elevada sobrevida a largo plazo.
Objetivo:
caracterizar los pacientes con MCPT en la clínica de Endocrinología y Metabolismo del Hospital de Clínicas en la década 2008-2018.
Materiales y métodos:
estudio observacional, transversal, retrospectivo y analítico. Se revisaron historias de archivo y policlínica de pacientes que concurrieron a nuestro servicio desde junio/2008 a junio/2018. Se recabó el número de pacientes atendidos en el hospital en 1978-2008 para estimar incidencia y casuística anual. Las asociaciones entre variables y de tendencias se analizaron estadísticamente.
Resultados:
de 193 pacientes con carcinoma diferenciado de tiroides, 42 (22%) tuvieron MCPT. La incidencia hospitalaria de MCPT tendió a aumentar en los últimos 40 años (media = 4,2 casos/año); 88% fueron mujeres. El 69% de los diagnósticos fue por punción aspiración de aguja fina (PAAF) de un nódulo tiroideo, siendo 57% unifocales y 43% multifocales. Hubo asociación significativa entre multifocalidad e invasión capsular. Un 84% no tuvo metástasis ganglionares. En 55% de los casos se realizó radioyodo (RY) postcirugía.
Conclusiones:
aumentó la incidencia de MCPT, mayormente en mujeres. El diagnóstico prequirúrgico se hizo fundamentalmente por PAAF de nódulos tiroideos. La invasión capsular se asoció a multifocalidad. Un 16% tuvo metástasis ganglionares al diagnóstico. En la mayoría se realizó tiroidectomía total y 55% RY.
... Notably, papillary thyroid carcinoma is often asymptomatic and incidentally detected in autopsy specimens (9)(10)(11)(12)(13)(14)(15). The highest prevalence ever reported of incidentally discovered papillary thyroid carcinomas in autopsies is 35.6% (9). ...
... Notably, papillary thyroid carcinoma is often asymptomatic and incidentally detected in autopsy specimens (9)(10)(11)(12)(13)(14)(15). The highest prevalence ever reported of incidentally discovered papillary thyroid carcinomas in autopsies is 35.6% (9). In Brazil, the frequency of this finding is estimated at 1%-8% (16). ...
... In Brazil, the frequency of this finding is estimated at 1%-8% (16). Some authors in Japan even consider these incidentalomas to be normal findings; for them, papillary microcarcinomas (tumors < 5 mm) do not require treatment and should only be followed up (9)(10)(11)(12)(13)(14)(15). Indeed, according to some specialists, single papillary thyroid microcarcinomas < 10 mm without lymph node metastases or extrathyroidal extension can be managed without surgical treatment and with active surveillance alone (16). ...
Objective:
The purpose of these guidelines is to provide specific recommendations for the surgical treatment of neck metastases in patients with papillary, follicular, and medullary thyroid carcinomas.
Materials and methods:
Recommendations were developed based on research of scientific articles (preferentially meta-analyses) and guidelines issued by international medical specialty societies. The American College of Physicians' Guideline Grading System was used to determine the levels of evidence and grades of recommendations. The following questions were answered: A) Is elective neck dissection indicated in the treatment of papillary, follicular, and medullary thyroid carcinoma? B) When should central, lateral, and modified radical neck dissection be performed? C) Could molecular tests guide the extent of the neck dissection?
Results and conclusion:
Recommendation 1: Elective central neck dissection is not indicated in patients with cN0 well-differentiated thyroid carcinoma or in those with noninvasive T1 and T2 tumors but may be considered in T3-T4 tumors or in the presence of metastases in the lateral neck compartments. Recommendation 2: Elective central neck dissection is recommended in medullary thyroid carcinoma. Recommendation 3: Selective neck dissection of levels II-V should be indicated to treat neck metastases in papillary thyroid cancer, an approach that decreases the risk of recurrence and mortality. Recommendation 4: Compartmental neck dissection is indicated in the treatment of lymph node recurrence after elective or therapeutic neck dissection; "berry node picking" is not recommended. Recommendation 5: There are currently no recommendations regarding the use of molecular tests in guiding the extent of neck dissection in thyroid cancer.
... Epidemiological data indicate that a higher incidence of autoimmune thyroid diseases is observed in people with a sufficient dietary iodine intake than in those with subclinical iodine deficiency [74]. On the other hand, chronic exposure to iodine in previously iodine-deficient patients with autoimmune thyroid disease may increase the risk of hypothyroidism and goiter, particularly in the short term [74]. ...
... Epidemiological data indicate that a higher incidence of autoimmune thyroid diseases is observed in people with a sufficient dietary iodine intake than in those with subclinical iodine deficiency [74]. On the other hand, chronic exposure to iodine in previously iodine-deficient patients with autoimmune thyroid disease may increase the risk of hypothyroidism and goiter, particularly in the short term [74]. It has been hypothesized that iodine exposure may trigger thyroid autoimmunity by exacerbating the immunogenicity of intrathyroidal iodized proteins, especially thyroglobulin [74]. ...
... On the other hand, chronic exposure to iodine in previously iodine-deficient patients with autoimmune thyroid disease may increase the risk of hypothyroidism and goiter, particularly in the short term [74]. It has been hypothesized that iodine exposure may trigger thyroid autoimmunity by exacerbating the immunogenicity of intrathyroidal iodized proteins, especially thyroglobulin [74]. Although some studies have demonstrated that iodine prophylaxis may increase the incidence of autoimmune thyroid diseases, other long-term trials have not confirmed that iodine prophylaxis reduces the incidence of hypothyroidism or that it does not increase the risk of hypothyroidism and thyroid autoimmunity [74]. ...
The thyroid gland requires iodine to synthesize thyroid hormones, and iodine deficiency results in the inadequate production of thyroxine and related thyroid, metabolic, developmental, and reproductive disorders. Iodine requirements are higher in infants, children, and during pregnancy and lactation than in adult men and non-pregnant women. Iodine is available in a wide range of foods and water and is susceptible to almost complete gastric and duodenal absorption as an iodide ion. A healthy diet usually provides a daily iodine consumption not exceeding 50% of the recommended intake. Iodine supplementation is usually necessary to prevent iodine deficiency disorders (IDDs), especially in endemic areas. The community-based strategy of iodine fortification in salt has eradicated IDDs, such as endemic goiter and cretinism, in countries providing adequate measures of iodine prophylaxis over several decades in the 20th century. Iodized salt is the cornerstone of iodine prophylaxis in endemic areas, and the continuous monitoring of community iodine intake and its related clinical outcomes is essential. Despite the relevant improvement in clinical outcomes, subclinical iodine deficiency persists even in Western Europe, especially among girls and women, being an issue in certain physiological conditions, such as pregnancy and lactation, and in people consuming unbalanced vegetable-based or salt-restricted diets. Detailed strategies to implement iodine intake (supplementation) could be considered for specific population groups when iodized salt alone is insufficient to provide adequate requirements.
... patients. Also these results are similar to the results of Costamagna et al. (17) , which revealed ITC in 53 (9.3%) patients out of 646 patients. Askitis et al. (21) revealed ITC in 33 (14.5%) of 228 patients. ...
... These small differences may be owing to their selection of patients who underwent only total thyroidectomy. In a study by Harach et al. (17) , the incidence ranged from 3-36 %. ...
... El cáncer de tiroides frecuentemente es asintomático, y su hallazgo ha sido comúnmente identificado en grandes estudios en los cuales se realizaron autopsias en pacientes que no presentaban enfermedad tiroidea conocida 15,16 . Se ha reportado una prevalencia de cánceres ocultos de tiroides de hasta un 30% en un estudio muy citado de Finlandia 15 , y en otros, tasas de CPT subclínico entre 5% a 30% 16 . ...
... Esto ha generado dudas sobre si la detección, el diagnóstico y el tratamiento de estos tumores resulta beneficioso para los pacientes. En conjunto, estos datos indican que la verdadera incidencia del carcinoma tiroideo subclínico es mucho mayor que la prevalencia de la enfermedad clínica [15][16][17][18] . ...
In recent decades, the increasing identification of thyroid nodules has led to a dramatic increase in the diagnosis and incidence rate of thyroid cancer. However, their mortality has remained stable. The largest fraction of this increase is attributable to the growing use of diagnostic technologies, which has identified an increasing number of mostly small, low clinical risk papillary thyroid cancers (PTC). Most of these tumors will not generate morbidity or mortality despite being untreated. Clinical practice has evolved towards a less aggressive treatment of PTC's. Active surveillance (AS) has emerged as a new therapeutic alternative within the treatment algorithm, which aims to recognize a potential minority group of patients in whom their thyroid papillary carcinoma will progress clinically, and therefore in whom surgical treatment will result in greater benefit than harm. In this review we aim to describe the epidemiology of papillary thyroid carcinoma, the concept of active surveillance in this area and the clinical results obtained by this therapeutic approach in the different experiences carried out in the world until now.
... The first experimental data on the existence of tumor cell reservoirs, which have little or no clinical significance, were obtained by Finnish pathologists [5]. Harach H.R. et al. showed that in 35.6% of thyroid autopsies of those who died from non-cancer causes, foci of "occult" papillary carcinoma could be detected. ...
Simple Summary
The COVID-19 pandemic caused a noticeable decrease in the number of cases of breast, prostate, renal, and thyroid cancers newly diagnosed in 2020 in the Russian Federation. There was no visible impact on mortality from these diseases. Mortality did not change during the pandemic and has remained at pre-pandemic levels until now. The detection rate returned to pre-pandemic levels during 2021–2022. One could speculate that the decrease in the number of newly diagnosed cases is due to cancer tests skipped during the lockdown. This is further evidence of the overdiagnosis of breast, prostate, renal, and thyroid cancers, which is linked to the mass testing of healthy populations.
Abstract
Overdiagnosis, associated with mass testing in healthy populations, is a significant issue for breast, prostate, renal, and thyroid cancers. During the lockdowns caused by the COVID-19 pandemic, the intensity of cancer screening was expected to go down. In this study, we analyzed the impact of the expected reduction in screening intensity on morbidity and mortality from certain malignancies. Cumulative data from the Russian National Cancer Registry available from 2000 to 2022 were analyzed. It was noted that there has been no noticeable effect of the COVID-19 lockdowns on mortality rates from breast, prostate, renal, or thyroid cancers. At the same time, the detectable incidence decreased markedly in 2020 at the time of the lockdowns and then returned to pre-pandemic levels in 2022. At the moment, there is no sufficient reason to believe that skipping screening tests in 2020 could have any impact on breast, prostate, renal, or thyroid cancer mortality two years later (2022). The data presented further confirm that the overdiagnosis of these types of malignancies is caused by widespread screening among a generally healthy population.
... In autopsy studies, the incidence of small PMCT varied from 1.0% to 35.6% [7][8][9][10]. Most of the autopsy series did not reveal differences in incidence with respect to gender, age, thyroid size, or multifocality [11,12]. ...
Background Papillary microcarcinoma thyroid (PMCT) accounts for around 85% of the thyroid malignancies. Most of the autopsy series did not reveal differences in incidence with respect to gender, age, thyroid size, or multifocality. With advances in ultrasonography and ne-needle aspiration biopsies, especially in mass screening programs, PMCT can be diagnosed before surgery. This study was conducted with the aim of understanding the determinants of PMCT. Methods A cross-sectional observational study was conducted at a surgery department. All patients diagnosed with PMCT in thyroidectomy specimen from 2003 to 2019 were studied. The case sheets and histopathology reports were retrieved from the computerised ling system. The case sheets and histopathology reports were retrieved from the computerised ling system. Results Out of the 140 cases studied there were 111 (79.0%) incidental cases and 29 (21.0%) non incidental cases of PMCT. Females were associated with higher chance of having incidental PMCT. Smaller size lesions were more associated with incidental PMCT. Conclusion Patients with the associated clinical risk factors should be observed carefully and periodically followed up. This can help in recognizing the occurrence of frank malignancy, the outcome of the disease and planning the appropriate timely management.
... However, there are constant controversies among scholars regarding the treatment strategies for low-risk PTMC [48][49][50], given that thyroidectomy often causes serious harm to patients, including damage to important adjacent structures such as the recurrent laryngeal nerve and parathyroid gland, leads to various mild or severe complications, scar residue, and cosmetic trouble, requires lifelong medication, afects the quality of life of patients to some extent, and requires a relatively high cost of resection [51][52][53][54]. A Finnish autopsy report showed that occult papillary carcinoma (≤5 mm) was a normal fnding and should not be blindly surgically removed [55]. Subsequently, many scholars raised objections to the adoption of immediate thyroidectomy for all low-risk PTMCs [56,57]. ...
Objective. To retrospectively evaluate the efficacy and safety of ultrasound-guided radiofrequency ablation (RFA) in the treatment of papillary thyroid microcarcinoma (PTMC) through a follow-up study of continuous postoperative surveillance and large-sample data. Methods. The efficacy of ultrasound-guided RFA was evaluated by measuring the tumor volume reduction rate (VRR), tumor disappearance rate, and disease progression in 358 patients with low-risk unifocal PTMC who underwent ultrasound-guided RFA at Hangzhou Weja Hospital, while the safety was evaluated by measuring their complications. Results. The VRR was −745.69 ± 1012.69 (%), −150.35 ± 395.5 (%), 46.47 ± 138.74 (%), 92.95 ± 27.88 (%), 97.78 ± 10.99 (%), and 99.27 ± 3.82 (%), respectively, at 1, 3, 6, 12, 18, and 24 months after RFA. The corresponding tumor disappearance rate was 1.68%, 9.78%, 43.85%, 82.68%, 92.59%, and 95.63%, respectively. No local recurrence, new tumors, lymph node metastasis, distant metastasis, and deaths caused by recurrent/metastatic PTMC were found at the last follow-up. Except for 3 cases (0.84%) with thickening or hoarseness of voice and 3 cases (0.84%) with coughing during drinking water, no other complications were found. Conclusions. Ultrasound-guided RFA has good efficacy and safety for the treatment of low-risk unifocal PTMC and can be promoted for use in patients who meet the required indications.
... This dramatic increase has been attributed mainly to the detection of indolent small thyroid cancers, particularly due to the widespread use of medical imaging, especially ultrasonography (US) [3,4]. Autopsy studies have also supported this finding, revealing that occult thyroid cancers were present in up to 35.6% of individuals who died from other causes [5]. Consequently, thyroid cancer has become a focal point in the debates surrounding overdiagnosis and overtreatment [6]. ...
The indolent nature and favorable outcomes associated with papillary thyroid microcarcinoma have prompted numerous prospective studies on active surveillance (AS) and its adoption as an alternative to immediate surgery in managing low-risk thyroid cancer. This article reviews the current status of AS, as outlined in various international practice guidelines. AS is typically recommended for tumors that measure 1 cm or less in diameter and do not exhibit aggressive subtypes on cytology, extrathyroidal extension, lymph node metastasis, or distant metastasis. To determine the most appropriate candidates for AS, factors such as tumor size, location, multiplicity, and ultrasound findings are considered, along with patient characteristics like medical condition, age, and family history. Moreover, shared decision-making, which includes patient-reported outcomes such as quality of life and cost-effectiveness, is essential. During AS, patients undergo regular ultrasound examinations to monitor for signs of disease progression, including tumor growth, extrathyroidal extension, or lymph node metastasis. In conclusion, while AS is a feasible and reliable approach for managing lowrisk thyroid cancer, it requires careful patient selection, effective communication for shared decision-making, standardized follow-up protocols, and a clear definition of disease progression.
... Thyroid gland involvement in TGDC Carcinoma ranges from 33%-45% [10], but this is misleading as the rate of incidental thyroid carcinoma being diagnosed on autopsy is also 30-35%. [13,14] However, total thyroidectomy can be performed to facilitate Radioactive Iodine Ablation (RIA), and hence various authors have recommended total thyroidectomy in addition to the Sistrunk procedure for TGDC carcinoma. [15,16,17] ...
This report elucidates a case of papillary carcinoma of the Thyroglossal Duct Cyst in a 19-year-old female. The swelling at presentation was suprahyoid, fixed and non-mobile with deglutition or tongue protrusion. Papillary carcinoma was diagnosed post-op through histopathological examination and a follow-up total thyroidectomy was planned. As the origin of TGDC papillary carcinoma is highly debated, no evidence-based guidelines yet exist as to the best line of treatment, however, Sistrunk’s procedure followed by total/near total thyroidectomy is widely considered the standard management practice in such cases.
... From the observation that the majority of new diagnoses of thyroid cancer were microcarcinomas [3] and that the presence of microcarcinomas was frequent in autopsy studies [18,19], it became apparent to researchers that incidental diagnosis plays an important role in the increasing incidence of disease. However, the degree of importance of incidental diagnosis in the disease is unknown, and the observation that more advanced tumors were also showing an increase in incidence [10][11][12][13] suggests the possibility that other factors could also be influencing this phenomenon. ...
Purpose: There is an ongoing debate about the reasons behind the increasing incidence of thyroid cancer in the last two to three decades. Here, we investigate how thyroid nodules were detected in a large series of consultations for thyroid nodular pathology. Methods: In total, 576 patients were analyzed, with a total
of 1014 nodules described. Results: In 347 (60.2%) cases, the diagnosis of a thyroid nodule was incidental, mostly during imaging tests for other reasons. Incidental diagnosis occurred among all ranges of nodule diameter and between palpable and non-palpable cases, even within a small proportion of symptomatic cases. In univariate analysis, incidental diagnosis was associated with smaller nodule
diameter, non-palpable nodules, asymptomatic cases, older patient age, less advanced stages (T1–2), and conservative management. After multivariate analysis, older age, euthyroidism, and smaller diameter were statistically significant. Incidental diagnosis contributed to the diagnosis of 53.8% of the cases of
cancer. Advanced T stages (T3–4) were more common in non-incidental diagnoses. Conclusion: Our results indicate that incidental diagnosis of thyroid nodules is a significant contributor to thyroid cancer diagnosis in all ranges of nodule diameter, especially at earlier stages
... Among the most significant epidemiology data, it was reported that more than 60% of the incidence of differentiated thyroid carcinoma (DTC) was linked to tumors smaller than 1 cm, exhibiting a consistently low mortality rate [3,7]. Additionally, the prevalence of occult thyroid microcarcinomas from necropsies have revealed rates reaching up to 35.6% [8][9][10]. This reinforced the concept that the majority of PMCs are commonly identified incidentally and does not entail substantial health or life risks [11][12][13][14]. ...
Active Surveillance is a non-invasive strategy designed to identify a minority of patients with low-risk papillary thyroid carcinoma who might experience clinical progression and benefit from additional definitive treatments. Global experience suggests that these tumors typically show minimal changes in size during active surveillance, often demonstrating very slow growth or even size reduction. Moreover, the rate of lymph node metastases is low and can be effectively managed through rescue surgery, without impacting cancer-related mortality. However, despite 30 years of experience demonstrating the safety and feasibility of active surveillance for appropriately selected patients, this approach seems to have limited adoption in specific contexts. This limitation can be attributed to various barriers, including disparities in access to accurate information about the indolent nature of this disease and the prevalence of a maximalist mindset among certain patients and medical settings. This review aims to revisit the experience from the last three decades, provide current insights into the clinical outcomes of active surveillance trials, and propose a systematic approach for its implementation. Furthermore, it intends to emphasize the importance of precise patient selection and provides new perspectives in the field.
... However, as patients diagnosed with TC could be treated by radical or subtotal thyroidectomy, a relatively slow increase in mortality risk was observed over the same period [27]. Furthermore, since the early-detected TC was predominantly benign or incidental tumour without great clinical significance, subsequent thyroid-replacement therapy and complications such as hypoparathyroidism and vocal-cord paralysis may pose new health risks to patients [28,29]. Notably, we observed favourable period effects in the past five years in Korea, which could be explained by the increased awareness about the impacts of overdiagnosis [30] and in accordance with our prediction analysis. ...
Background
The rising incidence of thyroid cancer (TC) has generated growing concern globally; yet there are no studies examining whether this incidence was followed by a rise in related mortality. We aimed to comprehensively quantify current trends and future projections of TC incidence and mortality, and to explore the association between the TC burden and socioeconomic inequality in different income strata.
Methods
We obtained incidence and mortality data on TC and population from the 2019 Global Burden of Disease (GBD) study and the United Nations’ World Population Prospects 2022. We applied an age-period-cohort (APC) model to estimate the overall annual percentage change (net drift) and age, period, and cohort effects from 1990 to 2019, and also constructed a Bayesian APC model to predict the TC burden through 2030.
Results
Over a third of global TC cases belonged to the high-income group. From 1990 to 2019, net drifts of TC incidence were >0 in all income groups, while a modest reduction (net drift <0) in mortality was observed in most income groups, except for the lower-middle-income group. Unfavourable age, period, and cohort effects were most notable in Vietnam, China, and Korea. The age-standardised incidence rate (ASIR) is predicted to increase whereas the age-standardized mortality rate (ASMR) is expected to decrease globally between 2020 and 2030, with geographic heterogeneity being detected across income groups. We observed a positive correlation between ASIR and universal health coverage index and health worker density, but a negative one between ASMR and the two indicators, primarily in upper-middle-income and high-income countries.
Conclusions
Opposite patterns in incidence and mortality of TC raise concerns about overdiagnosis, particularly in upper-middle-income and high-income countries. Discrepancies in the distribution of health service accessibility, including diagnostic techniques and therapeutic care, should be addressed by narrowing health inequalities in the TC burden across countries.
... The assessments of the presence of overdiagnosis have relied on indirect epidemiologic measures. For example, prior studies have examined incidental prostate, thyroid, and breast cancers found at autopsies to confirm the presence of a reservoir of subclinical cancers of these sites [1,[6][7][8]. Other studies have used incidence and mortality trends and lead-time estimates to infer the presence of overdiagnosis [9,10]. ...
Certain medical diagnoses and environmental or occupational exposures may be associated with elevated risk of cancer diagnosis, either through causal mechanisms or via increased detection of a subclinical reservoir through increased diagnostic scrutiny (overdiagnosis). The present study aimed to investigate the distribution of elevated cancer risks associated with different diagnoses and exposures. A systematic literature search was conducted to identify studies published in the last 30 years that examined the standardized incidence ratio (SIR) associated with exposures and risk factors. Meta-SIRs for each cancer type were calculated. The distribution of elevated cancer risks was then compared between cancer types previously reported to be susceptible to overdiagnosis and those that have not been associated with overdiagnosis. The review of 108 studies identified four patterns: SIR generally elevated for 1) only overdiagnosis-susceptible cancer types, 2) both overdiagnosed and non-overdiagnosed cancer types, 3) select cancers in accordance with risk factor or exposure, and 4) SIRs that did not exhibit a distinct increase in any cancer type. The distribution of elevated cancer risks may serve as a signature of whether the underlying risk factor or exposure is a carcinogenic process or a mechanism of increased diagnostic scrutiny uncovering clinically occult diseases. The identification of increased cancer risk should be viewed with caution, and analyzing the pattern of elevated cancer risk distribution can potentially reveal conditions that appear to be cancer risk factors but are in fact the result of exposure to medical surveillance or other healthcare activities that lead to the detection of indolent tumors.
... The natural history of these tumors often exhibits stability or slow-growing, or may even shrink [3]. This was illustrated by several autopsy studies worldwide showing a high rate of occult thyroid carcinomas, with a prevalence of up to 35.6% [5][6][7], representing 100 to 1000 times more than clinical carcinomas [8]. From another point of view, patients with papillary thyroid microcarcinomas (PMCs) who undergo total thyroidectomy, with or without radioiodine ablation, have a risk of recurrence at 10-12 years ranging from 0.5% to 1% for a single focus and increases to 5% when multiple foci or clinical lymph node metastases are initially diagnosed [9,10]. ...
The detection of low-risk thyroid carcinoma has increased in recent decades, although disease-specific mortality remained without changes. The high prevalence of occult carcinomas in autopsy studies, and hence the underlying indolent course of this entity, prompted the emergence of active surveillance as an alternative approach to these tumors. This strategy aims to recognize the minority group of patients who will develop clinical progression and probably benefit from deferred surgery. Experience around the world has shown that during active surveillance these tumors are mostly unchanged in size, with very-slow growth and even a decrease in diameter. Moreover, the rates of lymph node metastases were low and easily handled by rescue surgery, and distant metastases have not been reported. Given the high prevalence of small thyroid carcinomas and the excellent outcomes for observation, active surveillance provides a safe and feasible alternative in properly selected patients with low-risk thyroid cancer.
... In addition, despite the high incidence of thyroid cancer, the five-year survival rate of thyroid cancer in South Korea is 100% for both men and women [1]. Therefore, the possibility of overdiagnosis cannot be denied, considering the very high survival rate of thyroid cancer in South Korea, despite its increasing incidence [7,9,10]. Furthermore, patients diagnosed with thyroid cancer tend to prefer surgery over being placed under observation for further disease progression, even if the cancer is small in size and does not affect daily function [11]. ...
Background
South Korea has the highest incidence of thyroid cancer worldwide, raising questions regarding the possibility of overdiagnosis. Examining the factors affecting thyroid cancer screening is crucial in elucidating the reasons for this unusually high incidence of thyroid cancer. Therefore, in the present study, we investigated the association between breast cancer screening and thyroid cancer screening to determine the potential role of breast cancer screening in the overdiagnosis of thyroid cancer in South Korea.
Methods
We analyzed the data of women aged > 30 years who were enrolled in the 2014 Korean National Cancer Screening Survey. Self-reported breast cancer screening behavior was categorized as follows: no screening, mammography only, ultrasonography only, and both ultrasonography and mammography. Thyroid cancer screening behavior was categorized as follows: those who had or had not undergone ultrasonography screening. Logistic regression analysis was used to examine the associations between breast and thyroid cancer screening behaviors.
Results
Of the 2270 participants, a total of 569 (25.1%) were screened for thyroid cancer. Those who underwent only mammography, only ultrasonography, or both mammography and ultrasonography were more likely to be screened for thyroid cancer than those who did not undergo breast cancer screening (odds ratio [OR]: 1.47, 95% confidence interval [CI] 1.06–2.04; OR 2.71, 95% CI 1.83–4.02; OR 2.75, 95% CI 1.99–3.80, respectively).
Conclusions
Our findings indicate that thyroid cancer screening in Korea is likely to be performed on an opportunistic basis. Therefore, a nationwide public health and medical initiative is needed to curb the unnecessary use of thyroid screening in the asymptomatic general population.
... Through yet unknown mechanisms, dormant micro-metastases can transform into a fastgrowing state, resulting in disease recurrence. Therefore, understanding mechanisms that contribute to dormancy and/or escape from dormancy bears clinical significance, especially given the prevalence of dormant primary tumors (PTs) in the general population 7,8 , and dormant micro-metastases following PT excision 9,10 . ...
We recently showed that a minimally-invasive removal of MDA-MB-231HM primary tumors (PTs) and elimination of their secreted factors (including IL-6, IL-8, VEGF, EGF, PDGF-aa, MIF, SerpinE1, and M-CSF), caused regression of spontaneous micro-metastases into a non-growing dormant state. To explore the underlying mechanisms and potential clinical ramifications of this phenomenon, we herein used the MDA-MB-231HM human breast cancer cell-line, in-vitro, and in vivo following orthotopic implantation in immune-deficient BALB/C nu/nu mice. Employing bioluminescence imaging, we found that adding laparotomy to minimally-invasive removal of the PT caused an outbreak of micro-metastases. However, perioperative β-adrenergic and COX-2 inhibition, using propranolol+etodolac, maintained metastatic dormancy following laparotomy. In-vitro, β-adrenergic agonists (epinephrine or metaproterenol) and prostaglandin-E2 markedly increased MDA-MB-231HM secretion of the pro-metastatic factors IL-6, IL-8, and VEGF, whereas cortisol reduced their secretion, effects that were maintained even 12h after the washout of these agonists. In-vivo, laparotomy elevated IL-6 and IL-8 levels in both plasma and ex-vivo PT spontaneous secretion, whereas perioperative propranolol+etodolac administration blocked these effects. Similar trends were evident for EGF and MIF. Promoter-based bioinformatics analyses of excised PT transcriptomes implicated elevated NF-kB activity and reduced IRF1 activity in the gene regulatory effects of laparotomy, and these effects were inhibited by pre-surgical propranolol+etodolac. Taken together, our findings suggest a novel mechanism of post-operative metastatic outbreak, where surgery-induced adrenergic and prostanoid signaling increase the secretion of pro-metastatic factors, including IL-6, IL-8, and VEGF, from PT and possibly residual malignant tissue, and thereby prevent residual disease from entering dormancy.
... Autopsy studies provide additional evidence of overdiagnosis, with historical studies estimating occult thyroid cancer prevalence as high as 35% (21,22). LeClair and colleagues (22) compared papillary thyroid cancer (PTC) prevalence in autopsy studies with disease incidence in men and women in the SEER database. ...
Context
Low-risk differentiated thyroid cancer (DTC) is overdiagnosed, but true incidence has increased as well. Owing to its excellent prognosis with low morbidity and mortality, balancing treatment risks with risks of disease progression can be challenging, leading to several areas of controversy.
Evidence Acquisition
This mini-review is an overview of controversies and difficult decisions around the management of all stages of low-risk DTC, from diagnosis through treatment and follow-up. In particular, overdiagnosis, active surveillance versus surgery, extent of surgery, radioactive iodine (RAI) treatment, thyroid stimulating hormone suppression, and post-operative surveillance are discussed.
Evidence Synthesis
Recommendations regarding the diagnosis of DTC, the extent of treatment for low-risk DTC patients, and the intensity of post-treatment follow-up have all changed substantially in the past decade. While overdiagnosis remains a problem, there has been a true increase in incidence as well. Treatment options range from active surveillance of small tumors to total thyroidectomy followed by radioactive iodine in select cases. Recommendations for long-term surveillance frequency and duration are similarly broad.
Conclusions
Clinicians and patients must approach each case in a personalized and nuanced fashion to select the appropriate extent of treatment on an individual basis. In areas of evidential equipoise, data regarding patient-centered outcomes may help guide decision making.
... At present, the incidence rates of thyroid cancer are 7.4 and 22.0 per 100,000 for males and females in the United States (US), respectively (5). In addition, thyroid cancer is usually asymptomatic (6), and at autopsy, 35.6% of the Finnish population had occult thyroid cancer (7). Currently, most thyroid cancers are curable with conventional treatments such as surgery, radioactive iodide (RAI) therapy,thyroid stimulating hormone (TSH) suppression therapy for local or localized disease (8) and bioinformatics is also a useful tool to analyze sequencing results and clinical data, construct a prognostic model and seek involved pathways or therapeutic targets, particularly in tumor research (9)(10)(11). ...
Background
Accumulating evidence suggests that N6-methyladenosine (m6A) RNA methylation plays an important role in tumor proliferation and growth. However, its effect on the clinical prognosis, immune infiltration, and immunotherapy response of thyroid cancer patients has not been investigated in detail.
Methods
Clinical data and RNA expression profiles of thyroid cancer were extracted from the Cancer Genome Atlas-thyroid carcinoma (TCGA-THCA) and preprocessed for consensus clustering. The risk model was constructed based on differentially expressed genes (DEGs) using Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analyses. The associations between risk score and clinical traits, immune infiltration, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), immune infiltration, and immunotherapy were assessed. Immunohistochemistry was used to substantiate the clinical traits of our samples.
Results
Gene expression analysis showed that 17 genes, except YHTDF2, had significant differences (vs healthy control, P <0.001). Consensus clustering yielded 2 clusters according to their clinical features and estimated a poorer prognosis for Cluster 1 ( P =0.03). The heatmap between the 2 clusters showed differences in T ( P <0.01), N ( P <0.001) and stage ( P <0.01). Based on univariate Cox and LASSO regression, a risk model consisting of three high-risk genes (KIAA1429, RBM15, FTO) was established, and the expression difference between normal and tumor tissues of three genes was confirmed by immunohistochemical results of our clinical tissues. KEGG and GSEA analyses showed that the risk DEGs were related mainly to proteolysis, immune response, and cancer pathways. The levels of immune infiltration in the high- and low-risk groups were different mainly in iDCs ( P <0.05), NK cells ( P <0.05), and type-INF-II ( P <0.001). Immunotherapy analysis yielded 30 drugs associated with the expression of each gene and 20 drugs associated with the risk score.
Conclusions
Our risk model can act as an independent marker for thyroid cancer and provides promising immunotherapy targets for its treatment.
... Over 90% of thyroid malignancies are papillary carcinoma [1], with about 50% of these papillary thyroid microcarcinoma (PTMC) [2]. Due to the indolent nature of PTMC, traditional surgical treatment is not appropriate for all patients due to the risks of complications, surgical scar, loss of thyroid function, and adverse impact on quality of life are taken into account [3][4][5]. For these reasons, active surveillance (AS) has been proposed as an alternative strategy to surgery for patients with low-risk PTMC [6,7]. ...
Objective:
With the aim of standardizing and improving the use of ultrasound-guided PLA on PTMC, a panel of experts from China and Italy, jointly issued this expert consensus on the clinical use of PLA for low-risk PTMC.
Methods:
This expert consensus was developed by Chinese and Italian experts who have specific competence and expertise in this area. An evidence-based approach combining the knowledge and practical experience of the panelists was utilized.
Results:
Twenty-six expert consensus recommendations were developed, spanning topics including the indications and contraindications of PLA for PTMC, physician training, preoperative preparation of patients, intraoperative technical procedures, possible complications, efficacy assessment, follow-up strategy, the approach to new PTMC and metastatic lymph nodes after treatment, thyroid-stimulating hormone inhibition therapy, and quality control of the entire procedure.
Conclusion:
We summarized practical recommendations about standardized and improved PLA treatment for PTMC.
... Those have been reflected in several researches with an increase incidence in the last decade [14][15][16]. The coexistence among malignant neoplasm and autoimmune disease (AID) has been demonstrated; a particular group is the Systemic Erythematous Lupus (SEL) patients, the range of 0.4-3.4% the thyroid cancer was found in this people group as our results [17]. The autoimmune thyroid disease (ATD) as Hashimoto's thyroiditis (HT)or Graves Basedow disease could be a clinical manifestation of AID (ESL or Rheumatic Arthritis) [9,18]. ...
... This was confirmed by the study of Harach et al., which identified significant fibrosis in 79% of occult PTCs with an invasive growth pattern. Conversely, slight fibrosis was identified in circumscribed tumors [23]. Koperek et al. demonstrated that the three fibroblast activation markers α-SMA, FAP-α and Tn-C are highly expressed in the peritumoral and intratumoral stromal compartment of MTCs and that the expression of FAP-α and Tn-C correlates with the level of desmoplasia determined by histological analysis [21]. ...
Thyroid cancer is the most common type of endocrine cancer, and its prevalence continue to rise. Non-metastatic thyroid cancer patients are successfully treated. However, looking for new therapeutic strategies is of great importance for metastatic thyroid cancers that still lead to death. With respect to this, the tumor microenvironment (TME), which plays a key role in tumor progression, should be considered as a new promising therapeutic target to hamper thyroid cancer progression. Indeed, thyroid tumors consist of cancer cells and a heterogeneous and ever-changing niche, represented by the TME, which contributes to establishing most of the features of cancer cells. The TME consists of extracellular matrix (ECM) molecules, soluble factors, metabolites, blood and lymphatic tumor vessels and several stromal cell types that, by interacting with each other and with tumor cells, affect TME remodeling, cancer growth and progression. Among the thyroid TME components, cancer-associated fibroblasts (CAFs) have gained more attention in the last years. Indeed, recent important evidence showed that thyroid CAFs strongly sustain thyroid cancer growth and progression by producing soluble factors and ECM proteins, which, in turn, deeply affect thyroid cancer cell behavior and aggressiveness. Hence, in this article, we describe the thyroid TME, focusing on the desmoplastic stromal reaction, which is a powerful indicator of thyroid cancer progression and an invasive growth pattern. In addition, we discuss the origins and features of the thyroid CAFs, their influence on thyroid cancer growth and progression, their role in remodeling the ECM and their immune-modulating functions. We finally debate therapeutic perspectives targeting CAFs.
... Of 1773 studies screened, 99 full-text articles were reviewed, and 16 studies met the inclusion criteria (ranges: year of autopsy 1975-2005, age of decedents 16-75 years, 20-85% female; Fig. 1) (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). All but 3 studies analyzed consecutive autopsies, and across all included studies, only 6 decedents were excluded from original analyses due to history of thyroid cancer treatment. ...
Purpose
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 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 odds ratio of prevalence increasing by age group was 1.06 (0.92-1.2, p=0.37).
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.
... It was reported that, due to the indolence of PTC, most PTMC would either not progress or progress so slowly that it never leads to clinically meaningful disease over the patient's lifetime (8). In addition, the prevalence of occult PTC at autopsy in the general population was high, at 35.6% (9). Therefore, considering the very low disease-specific mortality and recurrence rates of PTMC and risk of surgical complications, the traditional management approach of immediate thyroid surgery for PTMC is being reconsidered (10). ...
Background
Overtreatment of papillary thyroid microcarcinoma (PTMC) has become a common concern. This study aimed to compare clinicopathological features between PTMC and papillary thyroid carcinoma (PTC) and to explore whether surgery can confer significant survival benefits in all patients with PTC or PTMC.
Methods
Data of 145,951 patients with PTC registered in Surveillance, Epidemiology, and End Results (SEER) database and 8,751 patients with PTC in our institution were retrospectively collected. Patients with tumors less than 10 mm in diameter were classified as PTMC cohort and the rest as PTC cohort. Clinicopathological features between PTMC and PTC were compared on the basis of SEER cohort and validated with institutional data. Survival analysis was conducted to explore the effect of surgery on the prognosis of patients. To minimize potential confounders and selection bias, we performed propensity score matching (PSM) analysis to match more comparable cohorts.
Results
Compared with PTC, PTMC exhibited the following characteristics: more common in women and whites, older age at diagnosis, lower proportion of follicular variants, intraglandular dissemination, extraglandular and capsular invasion, higher proportion of multifocality, fewer lymph node and distant metastases, and higher cancer-specific survival (CSS) and overall survival (OS) (all p -value < 0.05). Regarding treatment, patients with PTMC received a lower proportion of radiotherapy, chemotherapy, and total thyroidectomy but a higher proportion of lobectomy and/or isthmectomy. There was no significant difference in CSS for patients with PTMC at stage T1N0M0 with or without surgery ( P = 0.36).
Conclusion
Generally, PTMC showed higher biological indolence than PTC, which meant a higher survival rate for patients in both OS and CSS. For patients with PTMC at staged T1N0M0, active surveillance (AS) may be a potentially feasible management strategy. However, the maintenance of good medical compliance and the management of psychological burden cannot be ignored for patients included in AS.
... Since these nodules are not otherwise detected, if not symptomatic or picked up on screening, their prevalence in the general population comes only from autopsy studies, ranging from 2% to 36%. 25,26 In general, about one-third of the adult population may harbor indolent, sub-centimeter papillary thyroid carcinomas. 21 *For purposes of analysis the T2 group was split into two groups based on size. ...
Background: Early thyroid cancers have excellent long-term outcomes, yet the word “cancer” draws unnecessary apprehension. This study aimed to define when the recommendations for observation and surveillance may be extended to early thyroid cancers at the population level.
Methods: Non-metastasized thyroid cancers ≤40 mm diameter were identified from the 1975–2016 Surveillance, Epidemiology and End Results (SEER) database. Causes of death were compared across demographic data. Disease-specific outcomes were compared to the age-adjusted healthy United States (US) population. Survival estimates were computed using Kaplan–Meier and compared using the Cox proportional hazard model. Dynamic benchmarks impacting disease-specific overall survival were determined by decision tree modeling and tested by the Cox model.
Results: Of the 28,728 thyroid cancers included in this study, 98.4% underwent some form of thyroid-specific treatment and were followed for a maximum of 10.9 years. This group had a 4.3% mortality rate at the end of follow-up (10.9 years maximum), with 13 times more deaths attributed to competing risks rather than thyroid cancer (stage T1a versus stage T1b, P=1.000; T1 versus T2, P26 mm impacted outcomes.
Conclusion: Based on the current data, T1a and T1b nodules have similar survival outcomes and are not significantly impacted even when left untreated. Multi-institutional prospective studies are needed to confirm these findings so that current observation and surveillance recommendations can be extended to certain T1 thyroid nodules.
... prevalence of up to 30% in high-risk groups. [34] However, their clinical impact is limited in the vast majority of cases and do not cause a significant reduction in the survival. [35] In our study, we found that FNAC is a reliable method of screening thyroid nodules for PTC with a sensitivity as high as 86.7% and a positive predictive value of 93.6%. ...
Background: Papillary carcinoma thyroid is the most commonly occurring thyroid neoplasm which can be diagnosed by its characteristic cytological features by fine-needle aspiration procedure. Due too few limitations in fine-needle aspiration cytology (FNAC) technique, there are false-positive and false-negative diagnoses in papillary carcinoma thyroid lesions. Aim: In our study, we would like to evaluate the accuracy of thyroid FNAC and to determine the reasons for cytopathological discrepancies. Materials and Methods: Two hundred and twenty-three cases were collected from archives of our Department of Pathology. Slides were retrieved for which cytohistopathology correlation differed and reviewed. Statistical analysis for False positive/ negative rates, positive predictive value, sensitivity and specificity were done. Results: For 170 cases, cytohistopathology correlation, 27 cases were discordant which accounted for 15.2% of false-negative rates. 87% sensitivity, 96.6% positive predictive value and 10.6% false positive were calculated. Conclusion: FNAC is a reliable screening procedure in spite of having few pitfalls. Awareness of these pitfalls, while reporting by cytopathologist can minimize false-positive and false-negative reporting on thyroid lesions.
... Estas cifras apoyan la teoría de que el aumento de la incidencia de los CT es debido a un mayor diagnóstico de tumores de bajo riesgo como los mCPT [4,9]. Se ha observado una prevalencia de CT ocultos hasta en un 30% de necropsias, lo que indica que son tumores indolentes, muy probablemente mCPT [10,11]. También se ha observado una elevada prevalencia (>10%) de CT ocultos al examinar las glándulas tiroides extirpadas por enfermedades benignas [12]. ...
Introducción y objetivo: El número de pacientes con microcarcinoma papilar de la tiroides (mPTC) cada vez es más elevado. Las guías de práctica clínica han respaldado tanto la vigilancia activa como la cirugía como opciones de tratamiento para el (mCPT). En esta revisión nos planteamos como objetivo describir las opciones actuales de manejo del mCPT. Síntesis: La evidencia acumulada en los estudios realizados ha permitido conocer la historia natural y el comportamiento biológico de estos tumores. Mediante las extensas experiencias, se ha evidenciado que la gran mayoría de estos tumores muchas veces no presentan una variación significativa de su tamaño, o presentan tasas de crecimiento muy lentas, e incluso algunos presentan disminución de éste. La mayoría de mCPT son tumores de bajo riesgo clínico que no generarán morbilidad o mortalidad a pesar de no ser tratados. En los últimos años, la práctica clínica ha evolucionado hacia un tratamiento menos agresivo de estos mCPT para evitar la morbilidad derivada del tratamiento activo mediante cirugía y/o radioyodo y/o supresión hormonal. Los pacientes con tumores de alto riesgo deben ser manejados siguiendo los protocolos de los carcinomas papilares. Sin embargo, la vigilancia activa (VA) de pacientes con tumores de bajo riesgo ha mostrado excelentes resultados oncológicos sin aumentar la morbilidad y la mortalidad. Cuando se indica un tratamiento quirúrgico, la lobectomía es una opción válida para estos tumores. Los criterios de selección inicial para la idoneidad de ser manejados mediante VA deben tener en cuenta muchos aspectos, incluidas las características de los tumores y pacientes. En caso de alto riesgo de progresión deben ser sometidos a una cirugía inmediata en lugar de VA. Conclusiones: La VA ha surgido como una nueva alternativa terapéutica para estos tumores de bajo riesgo, con excelentes resultados oncológicos y menores tasas de complicaciones. No obstante, a pesar de los alentadores resultados de la VA, su implementación en la práctica depende de muchos aspectos entre los cuales se encuentran las características del tumor, las características clínicas del paciente y factores psicosociales.
... The prevalence of PTMC in autopsy studies is about 7-36%. [4,5] However, only a small proportion is significant enough to reach clinical attention. Besides, most patients are free of disease after the initial surgery, whether lobectomy or total thyroidectomy, even when radioiodine (RAI) therapy is not administered, suggesting an indolent nature of PTMC. ...
Background: Recent guidelines in the management of papillary thyroid microcarcinoma (PTMC) recommend limiting surgery. However, trends in the characteristics and management of PTMC from the Middle East and North Africa region is lacking.
Objectives: To determine the clinical features, management strategy, and outcomes of PTMC in a large tertiary care center in the United Arab Emirates (UAE).
Patients and Methods: This retrospective study included all patients diagnosed with PTMC (i.e., size ≤10 mm) at Tawam Hospital, Al Ain, UAE, between 2008 and 2019. Tumor histopathology, management strategy, and outcomes were the primary analyzed variables.
Results: A total of 213 patients with PTMC met the inclusion criteria, of which 83.6% were women and 58.7% were Emiratis. The majority had the classical tumor subtype (76.1%) and tumor of size 5–10 mm (71.4%). Multifocal disease was present in 41.1% and lymph node metastasis (LNM) in 16.6% of the patients. According to the 2015 American Thyroid Association categorization, the majority (93.9%) had a low-risk disease, and all except one patient had Stage 1 disease. Total thyroidectomy was performed in 91.1% of the patients, and 47.9% received radioiodine (RAI) therapy. None of the patients were under active surveillance strategy. RAI treatment was used more often in patients with non-incidental tumors, larger tumor size, multifocal disease, positive LNM, tumors in the intermediate/high ATA category, and those who underwent total thyroidectomy or neck dissection (for all, P < 0.05). After a median follow-up of 32.4 months, about 73% had an excellent response to dynamic risk stratification assessment, and only one patient had disease recurrence.
Conclusions: The majority of the patients had low-risk PTMC, yet most patients underwent total thyroidectomy, and almost 50% were treated with RAI ablation. Further studies are needed to determine if these trends are also present regionally and to explore reasons for not adopting a less aggressive approach in this indolent tumor.
... Papillary micro carcinoma is reported to be common incidental finding (25% or more, depending on the thoroughness of the examination) in thyroid glands removed for other reasons and in population-based autopsy studies. 10,11 However, recent studies show a prevalence of 2.1% probably owing to an over diagnosis due to improved imaging cytological modalities. 12 International agency of research on cancer has emphasized this issue in recent articles. ...
Background: Over the past few decades, the incidence of thyroid cancer has dramatically increased. Thyroid malignancy in multinodular goitre is considered to be high and these occult malignancies are detected only in post operative histopathological analysis. The study helps in finding association between multinodular goitre and thyroid malignancy. Objective was to find the association between multinodular goitre and thyroid malignancy in those who underwent total thyroidectomy.Methods: A cross sectional study conducted in department of general surgery, KIMS hospital, Bangalore. The 236 randomized cases of multinodular goitre who underwent total thyroidectomy were selected. Patients underwent thorough clinical examination pre operatively and were reassessed in post-operative period following surgery. Later, histopathology report on thyroidectomy specimen of the patients were obtained. This report was considered the gold standard for the diagnosis of thyroid malignancy.Results: Occult malignancies were commoner in middle aged females. Most of the patients in the study underwent total thyroidectomy. The prevalence of thyroid malignancy in our study was found to be 7.2%. In the study, 17 incidental malignancies were papillary carcinomas. It revealed a highly significant relation between the lymphocytic thyroiditis and occult malignancy (p<0.0001)Conclusions: The prevalence of malignancy in multinodular goitre is 7.2%. The only variant of incidental malignancy detected in histopathological examination of excised thyroid was papillary carcinoma. There is a statistically significant association between presence of thyroiditis in preoperative FNA and presence of occult malignancy carcinoma.
... Zunächst ist zu konstatieren, dass in unselektierten Autopsieserien etwa 2-5 % der untersuchten Schilddrüsen ein papilläres Schilddrüsenkarzinom aufwiesenabhängig von der Untersuchungstechnik überwiegend papilläre Mikrokarzinome (10)(11)(12). Diese messen definitionsgemäß < 1 cm und werden nach TNM als pT1a klassifiziert. ...
... Although the prevalence of palpable thyroid nodules is low (3%-4%) [1,2], incidental thyroid nodules are detected at a rate of 17%-67% with ultrasonography (US) [3][4][5][6], 16%-17% with neck computed tomography (CT) or magnetic resonance imaging (MRI) scans [7,8], 1%-2% with 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT scans [9,10], and 60% in autopsy specimens [11]. Thyroid malignancy was detected in 5% of patients with palpable thyroid nodules [12], in 8%-12% of non-palpable nodules evaluated using fine-needle aspiration (FNA) [13,14], and in 36% of the evaluated autopsy specimens [15]. Although the incidence of all sizes and stages of thyroid cancer, as well as thyroid cancerrelated mortality, has increased [16,17], early detection of low-risk small papillary thyroid carcinomas (PTCs) by US has contributed to the increased incidence of thyroid cancer over the last 20 years. ...
Incidental thyroid nodules are commonly detected on ultrasonography (US). This has contributed to the rapidly rising incidence of low-risk papillary thyroid carcinoma over the last 20 years. The appropriate diagnosis and management of these patients is based on the risk factors related to the patients as well as the thyroid nodules. The Korean Society of Thyroid Radiology (KSThR) published consensus recommendations for US-based management of thyroid nodules in 2011 and revised them in 2016. These guidelines have been used as the standard guidelines in Korea. However, recent advances in the diagnosis and management of thyroid nodules have necessitated the revision of the original recommendations. The task force of the KSThR has revised the Korean Thyroid Imaging Reporting and Data System and recommendations for US lexicon, biopsy criteria, US criteria of extrathyroidal extension, optimal thyroid computed tomography protocol, and US follow-up of thyroid nodules before and after biopsy. The biopsy criteria were revised to reduce unnecessary biopsies for benign nodules while maintaining an appropriate sensitivity for the detection of malignant tumors in small (1-2 cm) thyroid nodules. The goal of these recommendations is to provide the optimal scientific evidence and expert opinion consensus regarding US-based diagnosis and management of thyroid nodules.
... Some experts have raised concerns of overtreatment of small and indolent cancers that are unlikely to harm the patient if left untreated 26,30,31 . Frequent findings of previously undiagnosed thyroid microcarcinomas at post-mortem examinations [32][33][34] , are consistent with a probable accumulation of small tumours over time. These may be increasingly detected when neck ultrasonography and other sensitive diagnostic procedures are more widely used. ...
Background:
It is unclear whether the increasing incidence of thyroid cancer (TC) due to increased diagnosis of small and indolent tumours might mask a real increase of clinically significant cancers. The aim of this study was to correlate surgery, pathology and outcome data of individual patients to the mode of primary detection (palpation, by imaging or incidental) to assess if TC incidence has increased.
Methods:
The Swedish Cancer Registry identified all patients with TC in Västra Götaland County representing approximately 1.6 million inhabitants. Clinical information was retrieved from medical records of patient cohorts from three study intervals (2001-2002, 2006-2007 and 2011-2014) comprising 60 per cent of all TC patients. Data were also obtained from the NORDCAN registry to compare of TC incidence with other Nordic countries.
Results:
Between 2001 and 2014, the annualized standard incidence rate/100 000 population (ASR) of TC increased from 3.14 to 10.71 in women and from 1.12 to 3.77 in men. This was higher than the mean incidence for Sweden but similar to that in Norway and Finland. Differentiated TC (DTC) increased more than threefold. The majority of tumours (64 per cent) were detected by palpation. Larger tumours (10-20, 21-40 and greater than 40 mm) increased as much as microcarcinomas (less than 10 mm). Only 5 per cent of the tumours were detected by imaging. All disease-specific deaths (8.5 per cent of DTC in the first two cohorts) and most patients with recurrent or persistent disease (6.6 per cent of DTC cases) were diagnosed due to tumour-related symptoms.
Conclusion:
DTC in Western Sweden gradually increased between 2001 and 2014. The majority of tumours were detected by palpation suggesting a real increase in the incidence of clinically significant thyroid malignancies.
... A pesar de este aumento de la incidencia a nivel mundial, la mortalidad asociada a estos tumores se ha mantenido sin cambios significativos 4,5 . Por otro lado, estudios basados en autopsias han demostrado la presencia de CPT ocultos en hasta un tercio de los pacientes fallecidos por enfermedades no relacionadas con patologías tiroideas 6 . ...
The dramatic increase in the incidence of thyroid cancer in recent decades, which is primarily due to increased detection of papillary thyroid microcarcinomas (PTCM), has led to a significant increase in the costs associated with thyroid cancer care. Despite this increase in the worldwide incidence, the mortality associated with these tumors has remained unchanged. Consequently, several groups of researchers have suggested that low-risk papillary thyroid carcinomas (PTC) have been overdiagnosed and overtreated. Active surveillance (AS) has emerged as a new therapeutic alternative for these tumors, with excellent oncological results, lower complication rates, and which could help reduce economic costs. However, despite the encouraging results of AS, its implementation in practice depends on many aspects including the radiological characteristics of the tumor, the clinical characteristics of the patient, psychosocial factors and socioeconomic factors. In this review we will focus on describing the evidence accumulated to date regarding the natural history of PTC kinetics, cost effectiveness of VA, and current limitations to its implementation.
... Actually, papillary microcarcinomas (PMCs) represents the most diagnosed thyroid tumors, with a 35% incidence of occult papillary thyroid microcarcinomas in autopsy studies [5]. The increased diagnosis of these malignancies, associated with a low risk of recurrence and death, has led to the need for redefining of the multimodal therapeutic approach to avoid potential overtreatments. ...
Thyroid cancer is the most common endocrine malignancy, representing 2.9% of all new cancers in the United States. It has an excellent prognosis, with a five-year relative survival rate of 98.3%.Differentiated Thyroid Carcinomas (DTCs) are the most diagnosed thyroid tumors and are characterized by a slow growth rate and indolent course. For years, the only approach to treatment was thyroidectomy. Active surveillance (AS) has recently emerged as an alternative approach; it involves regular observation aimed at recognizing the minority of patients who will clinically progress and would likely benefit from rescue surgery. To better clarify the indications for active surveillance for low-risk thyroid cancers, we reviewed the current management of low-risk DTCs with a systematic search performed according to a PRISMA flowchart in electronic databases (PubMed, Web of Science, Scopus, and EMBASE) for studies published before May 2021. Fourteen publications were included for final analysis, with a total number of 4830 patients under AS. A total of 451/4830 (9.4%) patients experienced an increase in maximum diameter by >3 mm; 609/4830 (12.6%) patients underwent delayed surgery after AS; metastatic spread to cervical lymph nodes was present in 88/4213 (2.1%) patients; 4/3589 (0.1%) patients had metastatic disease outside of cervical lymph nodes. Finally, no subject had a documented mortality due to thyroid cancer during AS. Currently, the American Thyroid Association guidelines do not support AS as the first-line treatment in patients with PMC; however, they consider AS to be an effective alternative, particularly in patients with high surgical risk or poor life expectancy due to comorbid conditions. Thus, AS could be an alternative to immediate surgery for patients with very-low-risk tumors showing no cytologic evidence of aggressive disease, for high-risk surgical candidates, for those with concurrent comorbidities requiring urgent intervention, and for patients with a relatively short life expectancy.
... It has been recognized that microscopic colonies of cancer cells, termed dormant, latent, occult or in situ cancers, are found frequently in autopsied cases of individuals who did not have cancers during their lifetime. Specifically, over 30% of women had occult breast cancers at ages 40 to 50 years (Folkman and Kalluri 2004), and similar frequencies were reported for occult prostate cancers in Caucasian males aged over 60 (Jahn et al. 2015) and occult papillary thyroid cancers (OPC) (Harach et al. 1985). In the latter OPC study, since sectioning was done at 2-to 3-mm intervals while the majority of OPCs were below 1.0 mm in diameter, the number of OPCs over 0.15 mm in diameter was estimated to be about 300 among 36 thyroid samples. ...
[Purpose] Ionizing radiation is a well-known carcinogen, and epidemiologic efforts have been made to evaluate cancer risks following a radiation exposure. The basic approach has been to estimate increased levels of cancer mortality resulting from exposures to radiation, which is consistent with the somatic mutation theory of cancer. However, the possibility that an irradiation might cause an earlier onset of cancer has also been raised since the earliest days of animal studies. Recently, the mutation induction model has been challenged because it is unable to explain the observed dose-related parallel shift of entire mouse survival curves toward younger ages following an irradiation. This is because if it is assumed that only a fraction of the irradiated individuals are affected, the irradiated population would consist of two subpopulations with different mean lifespans, which makes the overall distribution of individual lifespans broader, and hence the slope of the survival curves shallower. To explain this parallel shift, it is necessary to assume that all individuals of a population are affected. As a result of these observations, possible mechanisms which could account for the parallel shift of mouse survival curves were sought by examining the radiation induction of various types of tissue damage which could facilitate an earlier onset of spontaneously arising cancers.
[Conclusion] A proposed mechanism postulates that a radiation exposure leads to tissue inflammation which subsequently stimulates spontaneously arising cancers and allows them to appear earlier than usual. This notion is not unprecedented, and because the background incidence of cancer increases exponentially with an increase in age, a slight shift of the onset age toward younger ages may make it appear as if the risk is increased. In this scenario, a radiation exposure induces DNA damage, cell death, chromosome aberrations etc., which leads to the multi-pathway responses including activation of stromal fibroblasts, macrophages and various inflammatory factors. Such an inflamed microenvironment favors the growth of spontaneously arising tumor cells although currently, the sequential order or relative importance of the individual factors remains to be known.
Biographical Note
Nori Nakamura PhD, is a radiation biologist and geneticist working at the Radiation Effects Research Foundation in Hiroshima, Japan, for more than 35 years. He is also interested in biodosimetry methods which include cytogenetic methods and the electron-spin (paramagnetic)-resonance method used to examine tooth enamel.
Background
There is limited evidence or agreement on the benefit, duration and frequency of post-operative surveillance neck ultrasound in patients with differentiated thyroid cancer treated with hemithyroidectomy alone. This study's primary aim was to assess the benefit of neck ultrasound in this situation, with a secondary aim to assess the detection of malignancy in the contralateral lobe in patients undergoing completion surgery.
Methods
A retrospective observational study was conducted involving patients who had differentiated thyroid cancer found at diagnostic hemithyroidectomy between 1 December 2013 and 31 December 2016.
Results
Of 105 patients, 74 underwent completion thyroidectomy. Thirty-five per cent of these patients had malignancy identified in the contralateral lobe, the majority were unsuspected sonographically. Of 31 hemithyroidectomy patients, 1 had a nodule classified as ‘U3’ (indeterminate) at the first ultrasound surveillance, ultimately identified as incidental papillary microcarcinomas on completion thyroidectomy. There was no other disease recurrence or malignancy at a median of 3.8 years’ follow up.
Conclusion
The findings indicate a limited role for ultrasound follow up of patients with differentiated thyroid cancer treated with hemithyroidectomy alone.
The incidence of papillary thyroid microcarcinoma （PTMC） increases rapidly. However, epidemiological and autopsy studies show that the prevalence of low-risk papillary thyroid microcarcinoma （LR-PTMC） is very high, but the mortality is very low. There is over-diagnosis and over-treatment for LR-PTMC. Active surveillance （AS） was adopted for LR-PTMCs instead of immediate surgery, and more than 70% of the lesions remained stable or shrank in clinical observation. Therefore, AS is recommended for LR-PTMCs in clinical guidelines of several academic organizations around the world. However, PTMC is not equal to low-risk cancer. The implementation of AS strategy requires a strict grasp of indications and full consideration of population characteristics to ensure the maximum benefit of patients. This paper summarizes the present clinical progress of active surveillance for adult LR-PTMC.
Introduction: pMCT is defined as a variant of papillary carcinoma that measures≤1 cm in diameter and which is characterized by an excellent prognosis. Recently, a proposal has been advanced to use the designation of papillary mirotumour (pMT) for pMCTs with no risk factors .
Aim: In this study, we aimed to reclassify pMCTs according to the Porto proposal(Pp) criteria.
Methods: We have retrospectively collected cases of pMCT diagnosed in our pathology department over a period of 10years(2012-2022). Clinical and pathological parameters have been retrieved from the patient’s medical records and pathological reports. We have evaluated all cases following the criteria of Pp. Cases that fulfilled all the criteria have been reclassified as pMT. We have briefly compared the clinical outcomes in both groups.
Results: 29 cases of pMCT was found. Mean age of patients was 46,6 years-old (17-67) with a female predominance (sex ratio=0,45). 23 cases of pMCT were incidentally discovered. The tumor was located in the right thyroid lobe in 15cases. The mean size of the tumor was 5,2mm. Multifocality was observed in 5 cases. A total of 17 cases could be classified as pMT according to the Pp. Only one patient developed pulmonary metastasis and local recurrence; however it was related to the papillary carcinoma firstly diagnosed in his contralateral lobe. Clinical outcome was also good in the group of papillary microcarcinoma (pMC) with no recurrence or distant metastasis.
Conclusion: According to the Pp,>50% of pMCT could be reclassified as pMT which could reduce the psychological impact and overtreatment. Further studies with large sample size and molecular analysis are however needed in order to definitively validate and generalize the use of Porto proposal.
Incidental findings (IFs) in the head & neck are a frequent challenge to the reporting radiologist. A combination of complex anatomy, widely varied imaging techniques and the high prevalence of benign pathology, makes safe and appropriate management of head & neck IFs problematic. The non-head & neck radiologist is unlikely to have prior personal experience of the relevant specialties or current involvement with the pertinent multidisciplinary teams, creating unfamiliarity with both the clinical aspects of head & neck disease and the value of examination techniques. This triumvirate of complex anatomy, pathology and imaging creates the perfect environment for excessive investigation and overdiagnosis. In this article, the most frequently encountered and clinically relevant head & neck IFs are summarised. To reflect daily clinical practice, we will firstly consider anatomic abnormalities identified on cross-sectional imaging and ultrasound, followed by a review of PET-CT incidental findings.
Background:
While female head and neck surgeons have made significant contributions to the field, women's achievements in scientific communication have traditionally been underreported.
Methods:
A search of high-impact journals in the field of head and neck surgery was performed in the Elsevier's Scopus database to identify the top 100 most-cited articles.
Results:
The top 100 most-cited articles (during the span of 1953 and 2016) had the highest total number of citations between 2005 and 2009. Women accounted for 36% of first authors and 25% of corresponding authors. Change in the relative number of first female authors in these top 100 articles did not increase significantly between 1950 and 2019.
Conclusion:
The proportion of female first authors in head and neck surgery has not significantly increased over the past several decades, despite greater numbers of female trainees. Our findings support the need for additional research on female representation in head and neck surgery.
The increase in small intrathyroid papillary thyroid cancer (PTC) observed worldwide over the past two decades, with no increase in cancer-specific mortality, has challenged the previous concept of total thyroidectomy as a one-size-fits-all panacea. After exclusion of papillary microcarcinomas, a systematic review of 20 clinical studies published since 2002, which compared hemithyroidectomy (HT) to total thyroidectomy (TT), found comparable long-term oncological outcomes for low-risk papillary thyroid cancer (LRPTC) 1–4 cm in diameter, whereas postoperative complication rates were markedly lower for HT. To refine individual treatment plans, HT should be combined with ipsilateral central lymph node dissection and intraoperative frozen section analysis for staging. Based on recent evidence from studies and in consideration of individual risk factors, patients with LRPTC can be offered the concept of HT as an alternative to the standard TT. A prerequisite for the treatment selection and decision is a comprehensive patient clarification of the possible advantages and disadvantages of both approaches.
Purpose of review:
This review discusses the current literature regarding low-value thyroid care in older adults, summarizing recent findings pertaining to screening for thyroid dysfunction and management of hypothyroidism, thyroid nodules and low-risk differentiated thyroid cancer.
Recent findings:
Despite a shift to a "less is more" paradigm for clinical thyroid care in older adults in recent years, current studies demonstrate that low-value care practices are still prevalent. Ineffective and potentially harmful services, such as routine treatment of subclinical hypothyroidism which can lead to overtreatment with thyroid hormone, inappropriate use of thyroid ultrasound, blanket fine needle aspiration biopsies of thyroid nodules, and more aggressive approaches to low-risk differentiated thyroid cancers, have been shown to contribute to adverse effects, particularly in comorbid older adults.
Summary:
Low-value thyroid care is common in older adults and can trigger a cascade of overdiagnosis and overtreatment leading to patient harm and increased healthcare costs, highlighting the urgent need for de-implementation efforts.
Objective
To investigate Incidental Thyroid Carcinoma (ITC) by comparing the results of Fine Needle Aspiration Biopsy (FNAB) cytology and the postoperative pathological findings.
Methods
Data of 1479 patients who underwent total thyroidectomy were retrieved. Three hundred eighty-six patients were excluded due to insufficient data. Each surgical specimen studied received two histopathological diagnoses: the local diagnosis ‒ for the same area in which the FNAB was performed; and the final diagnosis, which includes a study of the entire surgical specimen.
Results
A thousand and ninety-three patients were investigated. FNAB result was malignant in 187 patients, benign in 204, suspicious or indeterminate in 668 cases, and inconclusive in 34 cases. The prevalence of ITC was 15.1%. Most of the ITC in this series was less than 0.5 cm. The incidence of ITC was higher in Bethesda III (17.5% ITC) and IV (19% ITC) than in Bethesda II cases (1.5% false negatives and 9% ITC).
Conclusion
Although the incidence of false-negative results in Bethesda II nodules is only 1.5%, 9% of these patients had ITC in the thyroid parenchyma outside the nodule that underwent preoperative FNAB. The incidence of ITC in the same scenario was even higher in Bethesda III (17.5%) and Bethesda IV cases (19%). Ultrasonography-guided FNAB is an excellent method for the assessment of thyroid nodules. However, biopsy sites should be carefully selected. Despite the high incidence of incidentalomas, total thyroidectomy should not always be the treatment of choice due to its rare but potentially serious complications. The findings of the present study can assist future clinical decisions towards active surveillance strategies for the management of papillary thyroid carcinoma.
Differentiated thyroid cancers are more frequent in women than in men. These different frequencies may depend on differences in patient’s behavior and in thyroid investigations. However, an impact on sexual hormones is likely, although this has been insufficiently elucidated. Estrogens may increase the production of mutagenic molecules in the thyroid cell and favor the proliferation and invasion of tumoral cells by regulating both the thyrocyte enzymatic machinery and the inflammatory process associated with tumor growth. On the other hand, the worse prognosis of thyroid cancer associated with the male gender is poorly explained.
Background This study aims to determine the prediction performance of a machine learning-based clinical model for cervical lymph node metastasis (CLNM) in micropapillary thyroid carcinoma (MPTC) with ultrasound (US).
Methods Patients with MPTC who underwent total or hemithyroidectomy with unilateral or bilateral prophylactic central neck dissection were included (n = 692). Nodal status was pathologically determined. Clinical and US features and thyroid function markers were extracted to build a random forest model. A nomogram with the significant predictive risk factors from multivariable logistic regression analysis was built to visualize hazard rates. Finally, the predictive performances of the models were compared.
Results Overall, 332 patients (47.98%) had CLNM. In multiple logistic regression, the strong predictive risk factors for CLNM were younger age, larger anteroposterior diameter, lower anteroposterior/transverse diameter (A/T) ratio, and higher thyroglobulin (TG) concentration (P < 0.05). The random forest and nomogram models showed good predictive performance with the area under the curves (AUCs) of 0.836 and 0.780, respectively, which were significantly higher than those without A/T ratio in the models (AUCs: 0.807 vs. 0.722, all P < 0.05). The AUC of the A/T ratio as a single feature for predicting CLNM was 0.744, while A/T ratio (≤ 0.828) combined with anteroposterior diameter (≥ 10 mm) yielded a higher AUC of 0.754 for predicting CLNM.
Conclusions The machine learning-based clinical model with US had a good predictive performance for CLNM in MPTC patients. This clinical model may facilitate surgical decision-making for MPTC, especially regarding whether cervical lymph node dissection is warranted.
Surgical treatment of papillary thyroid microcarcinoma (PTMC) is evolving more and more into a controversial issue. As in Japan more than 50% of PTMCs are only observed, an increasing number of physicians in the western world are calling for active surveillance instead of lobectomy or total thyroidectomy. Unifocal carcinomas of older patients without extrathyroidal growth or lymph node involvement seem to be candidates for active surveillance. First estimations for a lifelong observation show that patients <30 years old will have a probability of tumor progression of more than 60%. A decision for surgery versus active surveillance has to weigh up all the arguments for and against, which have to be discussed and planned in detail together with the patient.
Importance
Thyroid cancer is more common in women than in men, but the associated causes of these differences are not fully understood.
Objective
To compare sex-specific thyroid cancer rates in the US to the prevalence of subclinical thyroid cancer at autopsy.
Data Sources
Data on thyroid cancer incidence and mortality by sex among US adults (≥18 years) were extracted from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program (SEER) data for 1975 to 2017. Embase, PubMed, and Web of Science databases were searched for studies on the prevalence of subclinical thyroid cancer at autopsy of men and women, from inception to May 31, 2021.
Study Selection
The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used to perform a systematic search for articles reporting the prevalence of subclinical thyroid cancer in autopsy results of both women and men. Of 101 studies identified, 8 studies containing 12 data sets met inclusion criteria; ie, they examined the whole thyroid gland, stated the number of thyroids examined, and reported results by sex. Excluded studies reported thyroid cancer in Japan after the atomic bombs or Chernobyl after the nuclear disaster; did not examine the whole thyroid gland or had incomplete information on thyroid examination methods; or did not report rates by sex.
Data Extraction and Synthesis
Thyroid cancer incidence and mortality data by sex, histologic type, and tumor size were extracted from SEER. The inverse variance heterogeneity model was used to meta-analyze the prevalence and the odds ratio of subclinical thyroid cancer by sex from 8 studies (12 data sets) on thyroid cancer prevalence in autopsy results.
Main Outcomes and Measures
Incidence and mortality of thyroid cancer, by histologic type and tumor size; prevalence of thyroid cancer in autopsy results.
Results
In 2017, 90% of thyroid cancers diagnosed were papillary thyroid cancer (PTC) and in 2013 to 2017, the women to men incidence ratio for small (≤2 cm) PTC was 4.39:1. The incidence ratio approached 1:1 as cancer type lethality increased. The ratio of thyroid cancer mortality by gender was 1.02:1 and remained stable from 1992 to 2017. Results of the meta-analysis showed that the pooled autopsy prevalence of subclinical PTC was 14% in women (95% CI, 8%-20%) and 11% in men (95% CI, 5%-18%). The pooled odds ratio of subclinical PTC in women compared with men was 1.07 (95% CI, 0.80-1.42).
Conclusions and Relevance
This cohort study and meta-analysis found that the belief that women get thyroid cancer more often than men is an oversimplification. The gender disparity is mostly confined to the detection of small subclinical PTCs, which are equally common in both sexes at autopsy but identified during life much more often in women than men. As the lethality of the cancer type increases, the ratio of detection by gender approaches 1:1. This phenomenon may be associated with gender differences in health care utilization and patterns of clinical thinking and can harm both women, who are subject to overdetection, and men, who may be at risk of underdetection.
Objective:
The incidence of papillary thyroid carcinoma (PTC) has increased in recent years and its treatment remains controversial. The objective of this study is to identify clinicopathological predictive factors of tumour recurrence.
Methods:
We retrospectively analysed 4,085 patients who underwent thyroidectomy for PTC from 1996 to 2015. Patients were stratified according to American Thyroid Association (ATA) risk categories and clinicopathological features were evaluated to identify independent factors for recurrence.
Results:
After a mean follow-up of 58.7 (range 3-256.5) months, tumour recurrence was diagnosed in 176 (4.3%) patients, mostly in lymph nodes. Distant metastasis occurred in 18 patients (0.4%). There were 3 (0.1%) cancer-related deaths. Multivariate analysis showed that tumour size >10 mm, multifocality, extrathyroidal extension and lymph node metastasis (all, P < 0.001) were independent risk factors for recurrence. Further, recurrence was identified in 1.6% of the ATA low-risk, 7.4% of the intermediate-risk and 22.7% of the high-risk patients (P < 0.001).
Conclusions:
In PTC patients, tumour size >10 mm, multifocality, extrathyroidal extension and presence of lymph node metastasis as well as the ATA recurrence staging system effectively predict recurrence.
Thorough examination of complete thyroid glands from 500 consecutive autopsies in a Swedish population revealed 43 primary thyroid carcinomas (8.6%). Thirty-two were papillary, seven follicular, and four medullary. All but three follicular carcinomas were less than 1 cm and clinically unsuspected. The prevalence of occult papillary carcinoma did not differ significantly between men and women and there was no definite increase in frequency with age in the age groups studied (40–90 years).
Thirty-nine (6.5%) latent thyroid carcinomas were found in 600 thyroid glands removed at autopsy in Oporto Medical School Laboratory of Pathology. The prevalence of latent thyroid carcinomas was significantly higher in women (sex ratio 4.3:1) and in elderly people (p less than 0.005) and appeared to be independent from the existence of another malignant neoplasm. The mean thyroid weight and the concurrent thyroid pathology of patients with thyroid carcinomas were not significantly different from those of patients without them. The study of cervical lymph nodes in the first 400 autopsies did not show any significant difference concerning histologic pattern, number of germinal centers and sinus histiocytosis between patients with thyroid carcinomas and those without them. Further investigation is required to evaluate the role of host factors on the peculiar characteristics of latent thyroid carcinomas.
A comparison of the incidence of the different histological types of thyroid carcinoma in an area of high dietary iodide and an area of normal iodide intake has been made. The areas chosen were Iceland and the region of Northeast Scotland centred on Aberdeen; both areas have clearly defined populations served by a single pathology laboratory. All definite and dubious thyroid carcinomas from both regions were examined and classified by the same two pathologists. The age-specific incidence rates for papillary carcinoma in surgical specimens in both areas rose with age; they were five times higher in Iceland (high iodide area) than in Northeast Scotland. The numbers of follicular carcinomas were small, and this tumor was relatively less frequent in Iceland than Aberdeen. These findings, together with the known high relative frequency of follicular carcinoma and low frequency of papillary carcinoma in areas of endemic goitre, lead to the suggestion that the incidence of papillary carcinoma and follicular carcinoma are separately influenced by dietary iodide, papillary carcinoma being high in areas of high iodide intake and low in areas with low dietary iodide. No evidence to implicate lymphocytic thyroiditis, radiation or genetic factors in the genesis of thyroid carcinoma in Iceland or Northeast Scotland was found in this study. Undifferentiated carcinoma was about three times as common in Iceland as in Northeast Scotland. Malignant lymphoma of the thyroid was suprisingly common in Northeast Scotland, possibly related to the high frequency of thyroiditis found in this region. These studies suggest that the incidence of different histological types of thyroid malignancy is influenced by different etiological factors. They also provide support for the subdivision of thyroid malignancy into these different types, and for the general importance of accurate histological typing in cancer epidemiology.
Thyroid glands obtained from patients in southeastern Canada, northeastern Japan, southern Poland, western Colombia, and from Japanese living in Hawaii were serially step-sectioned and examined microscopically using identical techniques and diagnostic criteria. The prevalence of occult papillary thyroid carcinoma was significantly higher in Japan (28.4%) and in Hawaiian Japanese (24.2%) when compared with Canada (6%), Poland (9.1%), and Colombia (5.6%). The carcinomas were all papillary except for a single follicular lesion from Colombia. There was no significant sex prevalence. Most of the patients were between 40 and 79 years of age, but there was no particular predominant decade. Only the Colombian series had a large number of younger patients, and they showed a slightly lower prevalence of occult carcinomas before age 40. Most papillary thyroid carcinomas grow slowly and probably remain occult for the life of the patient.
One hundred and seventy-nine primary malignant tumours of the thyroid seen at The London Hospital between 1945 and 1972 were classified by the system of Woolner et al. (1961) and Hazard (1964). The distinct pathological and clinical features of the differentiated primary carcinomas and the similarities and differences between malignant lymphoma and anaplastic carcinoma were confirmed. This study showed the 'benign' behaviour of more than half the 'differentiated' papillary and follicular carcinomas when treated by thyroid lobectomy and the very malignant nature of anaplastic carcinomas and lymphomas whatever their treatment. The behaviour of medullary carcinoma was closer to that of the other differentiated tumours than to the undifferentiated varieties. Our patients were not thought to have been exposed to known goitrogens or previous thyroid irradiation.
Five hundred and seventy-three thyroid tumors from surgical material and 161 autopsy cases were studied as to incidence, types, and precursor changes using the new WHO-classification. In the surgical material 225 tumors were follicular, 145 papillary, 147 anaplastic, 23 squamous cell, and 10 medullary. Twenty-three sarcomas were found. tthe percentage of follicular carcinoma had decreased, whereas that of papillary carcinoma increased and that of anaplastic carcinoma remained constant. In over 50% of anaplastic carcinomas neoplastic follicular structures have been identified. As a rule the more sections are prepared, the more papillary carcinomas and the less sarcomas are diagnosed. Thyroid tumors leading to death were found in 0.33% of 53,134 consecutive autopsies. Anaplastic (52.3%) and follicular (33.5%) carcinoma were most frequently encountered. Metastases of follicular and anaplastic carcinoma were most often found in the lung, pleura, and bones, whereas lymph nodes of the neck, lung, and bones were predominantly involved in cases of the papillary type. Therapy of thyroid carcinoma is total thyroidectomy. The transition of follicular carcinoma to the anaplastic type has to be avoided whenever possible.
All cases of thyroid cancer diagnosed in Finland in 1958-62 according to the Finnish Cancer Registry were re-examined and re-classified histologically. All the carcinomas in which papillary structures were seen regardless of the presence of follicular or solid areas as well, and also the rare purely follicular tumors with so-called ground-glass nuclei were classified as papillary carcinoma. The follicular carcinomas comprised the non-papillary carcinomas in which follicular or trabecular structures were seen and in which the nuclei were not of ground-glass type. There were 100 papillary and 60 follicular carcinomas. The histologic types differed in age and sex distribution, course of the disease and survival. The female:male ratio of the age-adjusted incidence rates was 3.3 for papillary but only 1.2 for follicular carcinoma. Papillary carcinoma occurred in all age groups, but the follicular type only in middle and old age. Regional lymph node metastases were common (42%) and distant metastases rare (14%) in papillary carcinoma. The situation was reversed in follicular carcinoma (2% and 72%). The survival rates were significantly higher for papillary than for follicular carcinoma. The relative 5-year rates were 83% and 54%. Papillary and follicular carcinoma appear to be two biologically different tumors with no intermediate or mixed forms. Therefore, they should be distinguished in clinical and in scientific work.
56 thyroid gland tumours and non neoplastic alterations were studied for keratin and thyroglobulin staining, using the indirect immunoperoxidase method on serial formalin fixed paraffin embedded sections. Papillary carcinomas showed a strong reaction with anti-keratin serum but a weak reaction with anti-thyroglobulin serum. Follicular adenomas and carcinomas showed virtually no reaction for keratin but a strong reaction for thyroglobulin. Undifferentiated and medullary carcinomas did not react with either antiserum, except for single cells in two undifferentiated carcinomas which reacted with anti-keratin serum. In nodular goiters, hyperplastic follicles showed little or no reaction with anti-keratin serum and strong reaction with anti-thyroglobulin serum. It is suggested that this virtually type-specific staining for keratin or thyroglobulin may be related to different degrees of cellular differentiation and organelle content in the tumour cells.
The presence of intermediate filament proteins of cytokeratin/prekeratin type and vimentin type was evaluated in non-neoplastic thyroid glands and in different types of thyroid neoplasms. Follicular epithelium of both normal and goitrous thyroids showed a strong reaction with anticytokeratin antibodies that widely cross-react with various simple epithelia. On the other hand, in normal thyroid, there were only occasionally (in one of 12 cases) solitary cells reacting with antibodies to epidermal prekeratin. In nodular goiters, such cells were often seen (eight of 18), especially among the lining cells of cysts, and in chronic thyroiditis in all (12 of 12) cases. Only the stromal cells and intraluminal macrophages reacted with antibodies to vimentin. Neoplastic cells of papillary carcinomas showed a positive staining reaction both with antibodies to cytokeratins and to epidermal prekeratin. Follicular carcinoma cells, although positive for cytokeratins, could generally not be stained with antibodies to epidermal prekeratin. Medullary carcinoma cells also showed cytokeratin positivity and, only occasionally, positivity for epidermal prekeratin. Anaplastic carcinomas were also reactive with antibodies to cytokeratin but, for the most part, were negative for epidermal prekeratin. Interestingly, some neoplastic cells of all types of thyroid carcinomas also appeared to contain vimentin, as shown with both polyclonal and monoclonal antivimentin antibodies. In contrast to carcinomas, the intermediate filaments of thyroid sarcomas and lymphomas were only of vimentin type. Furthermore, it was found that the papillary structures in benign goiters were only reactive with cytokeratin antibodies and lacked, in contrast to papillary carcinomas, epidermal prekeratin-like immunoreactivity. Hence, the analysis of intermediate filament proteins of thyroid tumors can be utilized to differentiate between papillary and follicular carcinomas and between benign and malignant papillary lesions as well as between anaplastic thyroid carcinomas and sarcomas or lymphomas.
Occult papillary carcinoma (OPC) of the thyroid, defined as a tumor less than 1.5 cm in diameter, often has regional lymph node metastases, while distant metastases have been regarded as practically nonexistent. We describe an OPC in which the first clinical manifestation was a lung metastasis.
Papillary carcinoma of the thyroid has been classically defined on the basis of the presence and even the predominance of papillary formations within the tumor. Changes in this traditional concept have evolved along two separate but related lines. The first is the realization that well-differentiated tumors having a papillary component, however minimal, will exhibit the behavior of papillary carcinoma even in the presence of extensive areas with a sclerosing, solid, or follicular pattern of growth. The second is an increased reliance on cytologic criteria (particularly the ground-glass nucleus) rather than architectural features for the identification of papillary carcinoma. Through the use of these criteria in association with various clinical features, evidence is put forward in support of the concept of a follicular variant of papillary carcinoma, i.e., a tumor type in which papillae are nil or absent but which still belongs by cell type and clinicopathologic behavior to the group of papillary carcinomas.
In order to determine the incidence of different morphological types of thyroid cancer in the Nordic countries, all cases of thyroid cancer reported to the national cancer registries of Finland, Iceland, Norway and Sweden over periods ranging from 1 to 14 years were re-examined (a total of 706 cases) by one or two pathologists from each country. The age-adjusted incidence rate for Iceland was clearly higher than those for the other Nordic countries. The rate for Finland was the lowest, and a five-fold difference was seen between Iceland and Finland. The differences in the incidence rates applied to all age groups and to both sexes. The differences also concerned all histological types and were more pronounced for papillary and medullary carcinomas. In papillary carcinoma, an almost 10-fold difference was found between Finland and Iceland. The causes of the differences are not known. There has been and probably still is some endemic goitre in Finland, Norway and Sweden, but no endemic goitre occurs in Iceland. Thus, no positive association was found between the presence of endemic goitre and the risk of follicular carcinoma. There was a marked negative association between endemic goitre and the risk of papillary carcinoma.
We have used ultrastructural techniques to study the pathogenesis of calcifications and psammoma bodies in human thyroid disorders. Particular attention was paid to psammoma bodies associated with papillary thyroid carcinoma which were found to represent the end stages of two different biologic events. The one event took place in the vascular stalk of the neoplastic papillae, starting with a thickening of the base lamina followed by a vascular thrombosis, calcification, and tumor cell necrosis. In the other, intralymphatic tumor thrombi in the thyroid adjacent to the main tumors or in the opposite thyroid lobe became necrotic and calcified. In some instances, destruction of the lymphy vessels led to fibrin exudation and perilymphatic fibrosis. The laminated bodies seen inside thyroid follicles in some nonneoplastic conditions were found to represent inspissated colloid and not considered to be true psammoma bodies. Like the amyloid calcifications seen in medullary carcinoma and the stromal calcospherites seen in several conditions, they seem to lack diagnostic importance. Our findings emphasize the biologic importance of the events leading to psammoma body formation and explain how they may contribute to the indolent course of this type of cancer.
Thorough examination of complete thyroid glands from 500 consecutive autopsies in a Swedish population revealed 43 primary thyroid carcinomas (8.6%). Thirty-two were papillary, seven follicular, and four medullary. All but three follicular carcinomas were less than 1 cm and clinically unsuspected. The prevalence of occult papillary carcinoma did not differ significantly between men and women and there was no definite increase in frequency with age in the age groups studied (40-90 years).
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