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Well-Differentiated Thyroid Carcinoma with Concomitant Hashimoto's Thyroiditis Present with Less Aggressive Clinical Stage and Low Recurrence
Abstract
Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are the most common differentiated thyroid cancers. Previous studies report that Hashimoto's thyroiditis (HT) concomitant with PTC is unusual and improves prognosis compared to classical PTC. Few previous studies address FTC concomitant with HT. In this study, we retrospectively analyzed data from one institution and compared clinical presentations and results of treatment of PTC and FTC with and without HT. In addition, studies comparing presentation and long term follow-up prognosis in classical PTC and FTC were conducted. A total of 1,788 PTC patients and 209 FTC patients underwent thyroidectomy with or without lymph node dissection and follow-up at Chang Gung Medical Center in Linkou, Taiwan. All thyroid carcinomas were pathologically classified according to World Health Organization criteria. Histological patterns of PTC were categorized as classical PTC, or PTC with HT. Follicular thyroid carcinoma patients were categorized as FTC or FTC with HT. The dataset contained a total of 1,703 PTC cases categorized as classical PTC, 85 cases of PTC with HT, 201 cases of FTC and eight cases of FTC with HT. Analysis of Classification of Malignant Tumors (TNM) stage revealed a higher percentage of classical PTC in stage IV than HT group (12.03% vs. 4.70%). Mean tumor size of classical PTC was larger than HT group. Although 42.3% of FTC cases presented with distant metastases, no cases of FTC with HT presented with distant metastasis. Cancer-specific mortality was higher in classical PTC group than in PTC with HT. There was 53.2% of FTC without HT assigned recurrent status, and six of them died of thyroid cancer. No cancer mortality or recurrence in HT with FTC. PTC and FTC with HT presented with better clinical stage and better prognosis after same therapeutic modality. In conclusions, both PTC and FTC with HT have less aggressive clinical presentation and better prognosis.
... Thyroid cancer is the most common endocrine malignancy, and papillary thyroid carcinoma (PTC) accounts for 80% to 90% of all thyroid cancer cases [3,4]. PTC is the most common type as well as the type showing the best clinical outcomes [5], and it is categorized as differentiated thyroid cancer (DTC) along with follicular thyroid carcinoma (FTC) [4,6]. ...
... Since Dailey et al. [11] first proposed the association between HT and PTC in 1955, many studies have suggested that HT is associated with the less invasive and less aggressive clinicopathologic features of PTC [10,12]. Furthermore, reports showing that HT is associated with a low recurrence rate of DTC shed light on the possibility that HT acts as a protective factor against poor prognosis of DTC [6,10,[13][14][15], but the effects of HT on the mortality from DTC have been rarely reported. Metaanalysis reported that HT reduces the risk for all-cause mortality in thyroid cancer [16,17], but no meta-analysis has been conducted on thyroid cancer-related mortality due to lack of data. ...
... The literature search yielded 277 studies. After the exclusion of 31 duplicate studies and 238 studies that did not meet the inclusion criteria, seven studies [6,[20][21][22][23][24][25] were finally included in the meta-analysis (Fig. 3). The characteristics of each study are summarized in Table 5. ...
Background:
Many studies have shown that Hashimoto's thyroiditis (HT) acts as a protective factor in differentiated thyroid cancer (DTC), but little is known about its effects on mortality. Therefore, this study was performed to reveal the prognosis of HT on mortality in patients with DTC.
Methods:
This study included two types of research results: retrospective cohort study using the National Epidemiologic Survey of Thyroid cancer (NEST) in Korea and meta-analysis study with the NEST data and eight selected studies.
Results:
Of the 4,398 patients with DTC in NEST, 341 patients (7.8%) died during the median follow-up period of 15 years (interquartile range, 12.3 to 15.6). Of these, 91 deaths (2.1%) were related to DTC. HT was associated with a smaller tumor size and less aggressive DTC. In Cox regression analysis after adjusting for age and sex, patients with HT showed a significantly lower risk of all-cause death (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52 to 0.96) and DTC-related death (HR, 0.33; 95% CI, 0.14 to 0.77). The analysis with inverse probability of treatment weight data adjusted for age, sex, and year of thyroid cancer registration showed similar association. The meta-analysis showed that patients with HT showed a lower risk of all-cause mortality (risk ratio [RR], 0.24; 95% CI, 0.13 to 0.47) and thyroid cancer-related mortality (RR, 0.23; 95% CI, 0.13 to 0.40) in comparison with patients without HT.
Conclusion:
This study showed that DTC co-presenting with HT is associated with a low risk of advanced DTC and presents a low risk for all-cause and DTC-related death.
... Prognosis Description References Mortality (+) Presence of ATA and the previous history of AID correlated negatively with the occurrence of death [45,56,[120][121][122] Recurrence / Persistence (+) Presence of ATA or the previous history of AID or concurrent CLT correlated negatively with the recurrence or persistent disease [45,[54][55][56][57][120][121][122][123][124][125] Extrathyroidal extension (+) Presence of concurrent CLT was associated with the absence of extrathyroidal extension [54,56,[126][127][128][129] Lymph-node metastasis (+) Presence of CLT was associated with the absence of lymph-node metastasis [54,126,[129][130][131][132][133][134][135] Tumor size (+) Presence of chronic lymphocytic thyroiditis was associated with smaller tumor size [54-56, 121, 123, 126-129, 132, 136-139] Capsular invasion (+) Presence of CLT was associated with the absence of capsular invasion [57,126] Gender (+) Presence of CLT was more frequent among women [54,55,123,125,126,128,129,132,134,137,[139][140][141][142][143][144]] Multifocality ( -) Presence of CLT was more frequent among multifocal tumors [60, 130, 132, 133, 136-138, 141, 142, 145, 146] TNM stage (+) Presence of CLT was associated with less aggressive stage [57,121,125,128,132,138,139,144,147] Age (+) Patients with chronic lymphocytic thyroiditis were younger [127,134,139,142,143] Content courtesy of Springer Nature, terms of use apply. Rights reserved. ...
... Prognosis Description References Mortality (+) Presence of ATA and the previous history of AID correlated negatively with the occurrence of death [45,56,[120][121][122] Recurrence / Persistence (+) Presence of ATA or the previous history of AID or concurrent CLT correlated negatively with the recurrence or persistent disease [45,[54][55][56][57][120][121][122][123][124][125] Extrathyroidal extension (+) Presence of concurrent CLT was associated with the absence of extrathyroidal extension [54,56,[126][127][128][129] Lymph-node metastasis (+) Presence of CLT was associated with the absence of lymph-node metastasis [54,126,[129][130][131][132][133][134][135] Tumor size (+) Presence of chronic lymphocytic thyroiditis was associated with smaller tumor size [54-56, 121, 123, 126-129, 132, 136-139] Capsular invasion (+) Presence of CLT was associated with the absence of capsular invasion [57,126] Gender (+) Presence of CLT was more frequent among women [54,55,123,125,126,128,129,132,134,137,[139][140][141][142][143][144]] Multifocality ( -) Presence of CLT was more frequent among multifocal tumors [60, 130, 132, 133, 136-138, 141, 142, 145, 146] TNM stage (+) Presence of CLT was associated with less aggressive stage [57,121,125,128,132,138,139,144,147] Age (+) Patients with chronic lymphocytic thyroiditis were younger [127,134,139,142,143] Content courtesy of Springer Nature, terms of use apply. Rights reserved. ...
... Prognosis Description References Mortality (+) Presence of ATA and the previous history of AID correlated negatively with the occurrence of death [45,56,[120][121][122] Recurrence / Persistence (+) Presence of ATA or the previous history of AID or concurrent CLT correlated negatively with the recurrence or persistent disease [45,[54][55][56][57][120][121][122][123][124][125] Extrathyroidal extension (+) Presence of concurrent CLT was associated with the absence of extrathyroidal extension [54,56,[126][127][128][129] Lymph-node metastasis (+) Presence of CLT was associated with the absence of lymph-node metastasis [54,126,[129][130][131][132][133][134][135] Tumor size (+) Presence of chronic lymphocytic thyroiditis was associated with smaller tumor size [54-56, 121, 123, 126-129, 132, 136-139] Capsular invasion (+) Presence of CLT was associated with the absence of capsular invasion [57,126] Gender (+) Presence of CLT was more frequent among women [54,55,123,125,126,128,129,132,134,137,[139][140][141][142][143][144]] Multifocality ( -) Presence of CLT was more frequent among multifocal tumors [60, 130, 132, 133, 136-138, 141, 142, 145, 146] TNM stage (+) Presence of CLT was associated with less aggressive stage [57,121,125,128,132,138,139,144,147] Age (+) Patients with chronic lymphocytic thyroiditis were younger [127,134,139,142,143] Content courtesy of Springer Nature, terms of use apply. Rights reserved. ...
The recent incorporation of immune checkpoint inhibitors targeting the PD-1 (programmed cell death receptor 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) pathways into the therapeutic armamentarium of cancer has increased the need to understand the correlation between the immune system, autoimmunity, and malignant neoplasms. Both autoimmune thyroid diseases and thyroid cancer are common clinical conditions. The molecular pathology of autoimmune thyroid diseases is characterized by the important impact of the PD-1/PD-L1 axis, an important inhibitory pathway involved in the regulation of T-cell responses. Insufficient inhibitory pathways may prone the thyroid tissue to a self-destructive immune response that leads to hypothyroidism. On the other hand, the PD-1/PD-L1 axis and other co-inhibitory pathways are the cornerstones of the immune escape mechanisms in thyroid cancer, which is a mechanism through which the immune response fails to recognize and eradicate thyroid tumor cells. This common mechanism raises the idea that thyroid autoimmunity and thyroid cancer may be opposite sides of the same coin, meaning that both conditions share similar molecular signatures. When associated with thyroid autoimmunity, thyroid cancer may have a less aggressive presentation, even though the molecular explanation of this clinical consequence is unclear. More studies are warranted to elucidate the molecular link between thyroid autoimmune disease and thyroid cancer. The prognostic impact that thyroid autoimmune disease, especially chronic lymphocytic thyroiditis, may exert on thyroid cancer raises important insights that can help physicians to better individualize the management of patients with thyroid cancer.
... Асоціація хронічного тиреоїдиту та ПК зустрічається частіше, ніж ХАІТ з іншими пухлинами ЩЗ [Мишуніна та ін., 2017; Cordioli et al., 2013;Huang et al., 2011;Konturek et al., 2013;Lee et al., 2013;Pagano et al., 2012;Zhang et al., 2014]. ...
... ності злоякісної пухлини на характеристики останньої є неоднозначними, причому вивчення асоціації супутньої тиреоїдної патології та злоякісних пухлин стосувалося і стосується в переважній більшості випадків ПК і впливу хронічного тиреоїдиту на її виникнення та формування агресивності [Bogdanova et al., 2018;Hampson et al., 2018;. Проте і ця інформація часто є суперечливою [Huang et al., 2011;Jara et al., 2013;Palaniappan et al., 2018;Zhang, Jiang, 2018], і, незважаючи на те, що частоту поширення хронічного тиреоїдиту, супутнього ПК, більшість дослідників вважає суттєвою, тісна кореляція між ними наразі ще викликає сумніви [Kalezic et al., 2013;Nagaiah et al., 2011]. Залишається з'ясувати, чи є хронічний тиреоїдит реактивною прозапальною відповіддю на існування карциноми, чи однією з умов ініціації канцерогенезу в ЩЗ . ...
Тронько М.Д., Гуда Б.Б., Пушкарьов В.М., Ковзун О.І., Терехова
Г.М., Пушкарьов В.В.
Рак щитоподібної залози: етіопатогенез, діагностика
та лікування: монографія. — Біла Церква: Час Змін Інформ,
2023. — 776 с., іл.
ISBN 978-617-7959-87-7
У монографії представлені результати власних досліджень
авторів та cучасні дані світової літератури щодо епідеміології, іс-
нуючих діагностичних підходів, прогнозу перебігу, класифікації
ризиків та стратегії лікування високодиференційованого раку
щитоподібної залози. Детально описані молекулярні механізми
патогенезу всіх типів карцином щитоподібної залози, головні
чинники які призводять до виникнення раку, процес та маркери
метастазування. Висвітлюються можливі механізми радіоінду-
кованого раку.
Частина роботи присвячена новим аспектам лікування од-
ного з найбільш агресивних типів раку людини – анапластичній
карциномі щитоподібної залози. Показаний механізм дії такса-
нів та їх взаємодії з іншими протипухлинними агентами. Наво-
дяться схеми лікування.
... Асоціація хронічного тиреоїдиту та ПК зустрічається частіше, ніж ХАІТ з іншими пухлинами ЩЗ [Мишуніна та ін., 2017; Cordioli et al., 2013;Huang et al., 2011;Konturek et al., 2013;Lee et al., 2013;Pagano et al., 2012;Zhang et al., 2014]. ...
... Водночас свідчення про вплив патологічних змін у позапухлинній тканині ЩЗ за наявності злоякісної пухлини на характеристики останньої є неоднозначними, причому вивчення асоціації супутньої тиреоїдної патології та злоякісних пухлин стосувалося і стосується в переважній більшості випадків ПК і впливу хронічного тиреоїдиту на її виникнення та формування агресивності [Bogdanova et al., 2018;Hampson et al., 2018;. Проте і ця інформація часто є суперечливою [Huang et al., 2011;Jara et al., 2013;Palaniappan et al., 2018;Zhang, Jiang, 2018], і, незважаючи на те, що частоту поширення хронічного тиреоїдиту, супутнього ПК, більшість дослідників вважає суттєвою, тісна кореляція між ними наразі ще викликає сумніви [Kalezic et al., 2013;Nagaiah et al., 2011]. Залишається з'ясувати, чи є хронічний тиреоїдит реактивною прозапальною відповіддю на існування карциноми, чи однією з умов ініціації канцерогенезу в ЩЗ . ...
Тронько М.Д., Гуда Б.Б., Пушкарьов В.М., Ковзун О.І., Терехова
Г.М., Пушкарьов В.В.
Рак щитоподібної залози: етіопатогенез, діагностика
та лікування: монографія. — Біла Церква: Час Змін Інформ,
2023. — 776 с., іл.
ISBN 978-617-7959-87-7
Дизайнер обкладинки Тетяна Виговська
У монографії представлені результати власних досліджень авторів та cучасні дані світової літератури щодо епідеміології, існуючих діагностичних підходів, прогнозу перебігу, класифікації ризиків та стратегії лікування високодиференційованого раку щитоподібної залози. Детально описані молекулярні механізми патогенезу всіх типів карцином щитоподібної залози, головні чинники які призводять до виникнення раку, процес та маркери
метастазування. Висвітлюються можливі механізми радіоіндукованого раку.
Частина роботи присвячена новим аспектам лікування одного з найбільш агресивних типів раку людини – анапластичній карциномі щитоподібної залози. Показаний механізм дії таксанів та їх взаємодії з іншими протипухлинними агентами. Наводяться схеми лікування.
УДК 616-006.04
ББК 55.6
ISBN 978-617-7959-87-7
© Тронько М.Д., Гуда Б.Б.,
Пушкарьов В.М.,
Ковзун О.І., Терехова Г.М.,
Пушкарьов В.В. текст, 2023
© ТОВ «Час Змін Інформ»,
оригінал-макет, 2023
Т73
... A number of studies have suggested that patients with PTC coexisting with HT could exhibit a better prognosis than those with PTC without HT. In a meta-analysis, Lee et al (2) considered that PTCs with coexistent HT had a tight association with a number of factors, such as the female sex, multifocality and high recurrence-free survival rates, which was confirmed in a study by Huang et al (21), which suggested that HT coexisting with PTC is associated with a favorable prognosis. Moreover, previous studies indicated that lymphocytic infiltration led to a low frequency of recurrence and an improvement in disease-free survival rate (22,23). ...
... The specific mechanism between HT in PTC and the host immune reaction remains unclear (21). It was reported that the balance between pro-inflammatory and anti-inflammatory factors, including IL-4 and IL-6, in PTC with HT is disrupted, which has a tendency to exacerbate the autoimmune response (29). ...
The aim of the present study was to evaluate the association between coexisting lymphocytic thyroiditis (LT) and the clinicopathological features of papillary thyroid carcinoma (PTC). The records of 458 patients with PTC who underwent a total thyroidectomy and lymph node dissection in Sir Run Run Shaw Hospital (Hangzhou, China) were analyzed. In accordance with the histopathology of thyroid parenchyma, the cases were divided into three groups, including Hashimoto's thyroiditis (HT), non-Hashimoto's type LT (NHLT) and no LT. Based on the histopathology, data on age, sex, maximum diameter of tumor, multifocality, extrathyroidal extension, metastatic lymph node size, extranodal extension and tumor grades in the different groups were analyzed and compared. The prevalence of coexisting LT was 29.0% (133/458), of which 7.6% (35/458) was HT and 21.4% (98/458) was NHLT. PTC concomitant with LT was significantly associated with female patients (95.5 vs. 70.2%; P<0.001), a lower rate of extrathyroidal extension and/or capsular invasion (25.6 vs. 39.7%; P=0.004), central lymph node metastasis (CLNM) ratio (10.71 vs. 17.37; P=0.014), higher number of dissected central lymph nodes (16.83 vs. 11.7; P<0.001), larger metastatic lymph nodes (0.66 vs. 0.46 cm; P<0.001), higher occurrence of multifocality (61.7 vs. 50.5%; P=0.029) and earlier pT stage (57.9 vs. 38.8%; P<0.001), regardless of the combined or separate consideration of HT and NHLT. Besides, LT was associated with multifocality [odds ratio (OR), 1.578; 95% confidence interval (CI), 1.046-2.382; P=0.030]. Furthermore, in patients with PTC, CLNM had a significant association with the male sex (OR, 2.000; 95% CI, 1.216-3.288; P=0.006), an age of <45 years (OR, 0.592; 95% CI, 0.398-0.879; P=0.009) and a tumor size of >1 cm (OR, 3.913; 95% CI, 2.431-5.734; P<0.001). In conclusion, patients with PTC and LT showed a greater female preponderance, multifocality, a lower extrathyroidal extension and a lower CLNM ratio. LT was associated with an increased risk of multifocality in PTC.
... The prevalence of chronic lymphocytic thyroiditis (CLT) in PTC patients ranges from 0.5% to 38% [14][15][16]. For DTC with lymphocytic thyroiditis, lower recurrence and mortality rates have been reported [16][17][18][19]. Various theories have been proposed to explain how the coexistence of CLT leads to a better prognosis in PTC. ...
Objective: The role of the tumor microenvironment in tumor progression and treatment response is being investigated for different types of cancer. This study aimed to determine the relationships between tumor microenvironment, histopathology, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)-based metabolic parameters, treatment response, and overall survival (OS) in metastatic differentiated thyroid cancer (DTC).
Methods: Metastatic DTC patients who underwent 18F-FDG PET/CT between 2015-2019 were evaluated. Clinicopathological, histopathological features and PET/CT parameters of patients were recorded. Microenvironmental characteristics of the primary tumor, such as mitosis, intratumoral and peritumoral lymphocytosis, intratumoral and peritumoral fibrosis, were evaluated from the tissue samples. The relationships between these factors were statistically analyzed.
Results: Sixty-five patients (38 females, 27 males, age: 49±15 years) were included. Mitosis, intra/peritumoral lymphocytosis, and intra/peritumoral fibrosis were frequent; however, none of them had a statistically significant association with PET-positive metastases, treatment response, or OS. Univariate analysis showed that gender, size, thyroglobulin values, residual thyroid tissue, PET-positive metastases, and maximum standardized uptake value (SUVmax) were significant predictors of OS. At multivariate analysis, PET-positive metastases (HR=-2.65, 95%CI 0.007−0.707, p=0.024) and SUVmax (HR=-2.74, 95%CI 0.006−0.687, p=0.023) were the only independent predictors for OS.
Conclusion: Our study revealed that microenvironmental characteristics of the primary tumor did not show prognostic significance in metastatic DTC. PET-positive metastases and SUVmax levels were the only significant factors that predicted overall survival in DTC. Supporting the results of our study with further studies with a larger sample size may be necessary to determine the relationship between the tumor microenvironment and prognosis in DTC.
... Papillary carcinoma is the most common neoplasm associated with HT and a recent meta-analysis reported the co-existence of PTC in 8% (only male population) to 36.4% (both male and female population) of surgically removed thyroid specimens with HT [211]. The prognostic correlates of PTC arising on HT are not yet well established: some studies report a good clinical outcome related to the small size, the reduced rate of extrathyroidal infiltration and lymph node metastases, and the lack of BRAF mutation [212,213], but others did not find any significant better prognosis in this group of patients, compared to non-HTassociated PTC [214]. Although a definite association of HT with a specific PTC subtype has not been demonstrated, the rare Warthin-like subtype of PTC mostly arises in the context of HT [215]. ...
A variety of inflammatory conditions may directly involve the endocrine glands, leading to endocrine dysfunction that can cause severe consequences on patients’ health, if left untreated. Inflammation of the endocrine system may be caused by either infectious agents or other mechanisms, including autoimmune and other immune-mediated processes. Not infrequently, inflammatory and infectious diseases may appear as tumor-like lesions of endocrine organs and simulate neoplastic processes. These diseases may be clinically under-recognized and not infrequently the diagnosis is suggested on pathological samples. Thus, the pathologist should be aware of the basic principles of their pathogenesis, as well as of their morphological features, clinicopathological correlates, and differential diagnosis. Interestingly, several systemic inflammatory conditions show a peculiar tropism to the endocrine system as a whole. In turn, organ-specific inflammatory disorders are observed in endocrine glands. This review will focus on the morphological aspects and clinicopathological features of infectious diseases, autoimmune disorders, drug-induced inflammatory reactions, IgG4-related disease, and other inflammatory disorders involving the endocrine system. A mixed entity-based and organ-based approach will be used, with the aim to provide the practicing pathologist with a comprehensive and practical guide to the diagnosis of infectious and inflammatory disorders of the endocrine system.
... One single-institution experience of 2444 PTC reported a recurrence rate of 14% over 25 years [32]. Other studies cited recurrence rates up to 30% [32,33]. Witte et al. reported the rate of recurrence in FTC in their cohort to be 43.5%, with the majority of these recurrences occurring within the first 3 years following surgery [31]. ...
Simple Summary
Hashimoto’s thyroiditis and BRAF-mutation are protective and risk factors for thyroid cancer aggressiveness, respectively. We assessed the influence of Hashimoto’s thyroiditis and its influence on recurrence in patients with BRAF-wild type and BRAF-mutant differentiated thyroid carcinoma. Hashimoto’s thyroiditis was determined to be an independent protective factor against recurrence only in patients with BRAF-wild type carcinomas.
Abstract
A recent work analyzing the concomitant factors BRAF mutation (risk factor) and Hashimoto’s thyroiditis (HT) (protective factor) found that the presence of HT reduced lymph node metastasis in BRAF-mutated papillary thyroid carcinoma. Whether this notion is upheld with respect to disease recurrence and differentiated thyroid carcinoma (DTC), however, is unknown. We aimed to investigate the effect of underlying HT in DTC patients and its influence on recurrence with a specific emphasis in BRAF-mutated tumors. A total of 469 patients were included. Patients were stratified according to BRAF and HT status. Multivariate regression analysis was conducted to determine protective and risk factors of disease recurrence in patients with DTC. HT was associated with less-aggressive carcinomas including more frequent microcarcinomas (HT: 45.0% vs. no-HT: 34.0%, p = 0.02), less lymph node involvement (HT: 16.4% vs. no-HT: 26.1%, p = 0.02), and less disease recurrence (HT: 2.9% vs. no-HT: 11.9%, p = 0.002). BRAF mutation was also significantly associated with higher rates of lymph node involvement (BRAF-mutant: 41.9% vs. BRAF-wild type: 14.6%, p < 0.001) and almost two times the rate of recurrence (BRAF-mutant: 14.9% vs. BRAF-wild type: 6.5%, p = 0.004). Underlying HT was the only protective factor determined, reducing the odds of developing recurrence by 70% (HR: 0.30, 95%CI: 0.11–0.88). In the BRAF-wild type cohort, regression analysis continued to determine HT as a protective factor (p = 0.03). However, in the BRAF-mutant cohort, HT was no longer an independent protective factor (p = 0.20) against recurrence. Sub-group regression analysis, including PTC patients, similarly found HT as a protective factor only in BRAF-wild type patients (p = 0.039) and not BRAF-mutant (p = 0.627). The presence of underlying HT is associated with less aggressive tumors and is an independent protective factor against DTC recurrence, reducing the risk by 70%. HT remains a protective factor in BRAF-wild type carcinoma, but not in patients with BRAF-mutant carcinoma. HT may potentially be considered as a parameter which enhances American Thyroid Association patient risk stratification.
Background:
Papillary thyroid carcinoma (PTC) is an indolent disease with favorable outcomes. The non-surgical treatment approach known as active surveillance (AS) has been introduced as an alternative treatment instead of the traditional thyroidectomy. However, 10-15 % of PTC tend to progress. We sought to determine factors predicting the progression of PTC under AS.
Methods:
A systematic search was performed in January 2022 using PubMed, Embase, Google Scholar, Web of Science, and ScienceDirect. PRISMA guidelines were used by multiple reviewers to extract study characteristics (author name, publication date, journal name, country, institution, and study design), as well as main outcomes and measures. A combination of utilization of thyroid replacement therapy, baseline tumor size and volume, follow-up tumor size and volume, and the presence of lymph node metastasis and its distribution, as well as surveillance duration, were the main measures of this study.
Results:
Nine studies with 4166 patients were included, of which 354 showed tumor progression during AS (15 %; 95%CI = 7 % - 23 %). The average follow-up period was 41.58 months. The mean tumor maximum diameter was 8.54 mm (95%CI = 7.04-10.03). Tumor progression was most commonly secondary to an increase in volume by ≥50 % (75 %; 95%CI = 68 % - 80 %), then increase in diameter by ≥3 mm (41 %; 95%CI = 13 % - 76 %), and finally the development of lymph node metastasis (13 %; 95%CI = 9 % - 19 %). Approximately only 2 % of all patients thus developed new lymph node metastasis. Patient age, sex, and tumor size were not associated with higher risks of tumor progression. 12 % of AS patients eventually underwent surgery, though only 40 % (95%CI = 27 % - 53 %) of these patients displayed tumor progression.
Conclusions:
Our meta-analysis determined a tumor progression rate of 15 % in patients who underwent AS management, 13 % of which (2 % of all patients) developed lymph node metastasis. We found no protective or risk factors for tumor progression, and that almost half of all patients who underwent delayed surgery did so for reasons other than tumor progression. While not biopsying small (<1 cm) or very low suspicious nodules is already recommended, AS may be an appropriate treatment option in patients appropriately counseled, considering the low risk of advanced tumor progression but also the considerable patient population who fail to adhere to treatment. Alternatively, in aim of preventing overtreatment in patients who would rather take proactive measures against their low-risk carcinoma, minimally-invasive ablation techniques may be an attractive option.
The controversy on whether or not inflammatory infiltrates in chronic lymphocytic thyroiditis predispose to cancer, has now merged into a debate over the role of the inflammatory infiltrates. The question is how and why some cells become transformed and what factors allow them to spread and in some cases become invasive. Here, we show that the amount of inflammatory mediators such as nitric oxide (NO) and high mobility group Box 1 protein (HMGB1) produced in thyroiditis microenvironment increases in tumors and could be involved in the cellular transformation process. NO and HMGB1 are known to attract macrophages that would promote angiogenesis, matrix remodelling and suppression of an efficient immune response. Inflammatory infiltrates could increase the risk of papillary cancer in patients with autoimmune lymphocytic thyroiditis. Cytokines and soluble inflammatory mediators involved in cancer-related inflammation are not only a target for innovative diagnostic and therapeutic strategies but they also represent a future challenge for oncologists.
This study investigated the utility of BRAF mutation testing of thyroid fine-needle aspiration biopsy (FNAB) specimens for preoperative risk stratification in papillary thyroid cancer (PTC).
We assessed the T1799A BRAF mutation status in thyroid FNAB specimens obtained from 190 patients before thyroidectomy for PTC and its association with clinicopathologic characteristics of the tumor revealed postoperatively.
We observed a significant association of BRAF mutation in preoperative FNAB specimens with poorer clinicopathologic outcomes of PTC. In comparison with the wild-type allele, BRAF mutation strongly predicted extrathyroidal extension (23% v 11%; P = .039), thyroid capsular invasion (29% v 16%; P = .045), and lymph node metastasis (38% v 18%; P = .002). During a median follow-up of 3 years (range, 0.6 to 10 years), PTC persistence/recurrence was seen in 36% of BRAF mutation-positive patients versus 12% of BRAF mutation-negative patients, with an odds ratio of 4.16 (95% CI, 1.70 to 10.17; P = .002). The positive and negative predictive values for preoperative FNAB-detected BRAF mutation to predict PTC persistence/recurrence were 36% and 88% for overall PTC and 34% and 92% for conventional PTC, respectively.
Preoperative BRAF mutation testing of FNAB specimens provides a novel tool to preoperatively identify PTC patients at higher risk for extensive disease (extrathyroidal extension and lymph node metastases) and those who are more likely to manifest disease persistence/recurrence. BRAF mutation, as a powerful risk prognostic marker, may therefore be useful in appropriately tailoring the initial surgical extent for patients with PTC.
The controversy on whether or not inflammatory infiltrates in chronic lymphocytic thyroiditis predispose to cancer, has now merged into a debate over the role of the inflammatory infiltrates. The question is how and why some cells become transformed and what factors allow them to spread and in some cases become invasive. Here, we show that the amount of inflammatory mediators such as nitric oxide (NO) and high mobility group Box 1 protein (HMGB1) produced in thyroiditis microenvironment increases in tumors and could be involved in the cellular transformation process. NO and HMGB1 are known to attract macrophages that would promote angiogenesis, matrix remodelling and suppression of an efficient immune response. Inflammatory infiltrates could increase the risk of papillary cancer in patients with autoimmune lymphocytic thyroiditis. Cytokines and soluble inflammatory mediators involved in cancer-related inflammation are not only a target for innovative diagnostic and therapeutic strategies but they also represent a future challenge for oncologists.
THE SIMULTANEOUS occurrence of a neoplasm and Hashimoto disease (Hashimoto "thyroiditis," lymphadenoid goiter, struma lymphomatosa) in a thyroid gland has been noted infrequently. In a study concerned primarily with the clinical aspects and pathogenesis of various types of thyroiditis, a significant statistical relation was found between malignant thyroid neoplasms and Hashimoto disease of the thyroid gland. Thirty-seven malignant neoplasms were observed in 302 glands which also displayed the characteristic lesions of Hashimoto disease, a frequency which would occur by chance less than 1 time in 1,000.1
The present study was concerned with 73 patients who had benign or malignant thyroid epithelial neoplasms associated with Hashimoto disease of the thyroid gland. Included in the study for comparative purposes were 207 patients who had only benign or malignant thyroid epithelial neoplasms and 205 patients who had Hashimoto disease without thyroid neoplasms (Table 1). All patients were observed during the last 10
Background:
An association between lymphocytic thyroiditis and thyroid papillary carcinoma is still controversial. To determine a definite statistical relation, a histopathologic study was performed on tissues from in three races, because there is a racial and age-related difference in the susceptibility to thyroiditis.
Methods:
The prevalence and severity of thyroiditis combined with adenomatous goiter, follicular adenoma, or papillary carcinoma was defined by examination of surgically resected materials from Japanese (626 patients), and white and African Americans (330 and 90 patients, respectively).
Results:
The prevalence of lymphocytic infiltrates, which are indicative of autoimmune thyroiditis, was significantly higher in patients with papillary carcinoma than in patients with adenomatous goiter or follicular adenoma among Japanese females (63.0%) and males (50.0%), white females (76.0%), and African American females (46.2%). Lymphocyte infiltration into the follicular adenoma or papillary carcinoma correlated with the severity of combined thyroiditis.
Conclusion:
An association between chronic lymphocytic thyroiditis and papillary carcinoma was confirmed in the Japanese, and white and African American populations. The possibility of autoimmune thyroiditis as a predisposing factor for papillary thyroid carcinoma, is suggested.
The risk of thyroid carcinoma in patients with thyroid nodules associated with Hashimoto's thyroiditis (HT) is a debatable issue. The studies defining the true risk of thyroid malignancy are scanty and mainly depend on retrospective series. To eliminate inherent bias of retrospective studies, this prospective study was carried out to evaluate the true malignancy rate of unselected thyroid nodules in patients with HT who underwent fine-needle aspiration cytology (FNAC).
These prospective data were gathered on all patients newly diagnosed with thyroid nodules who were sent for FNAC between May 2006 and August 2009. All patients were evaluated for the presence of HT diagnosis by measuring thyroid autoantibodies. If a patient had at least one positive thyroid autoantibody, then the patient was defined as HT with thyroid nodules. There were 164 patients (147 women and 17 men) with thyroid nodules associated with HT (HT group). There were 551 patients (432 women and 119 men) with thyroid nodules without HT (control group). All patients underwent FNAC and ultrasonography (US).
The malignancy rate was 1.0% in HT group (2 out of 191 nodules) and 2.7% in the control group (19 out of 713 nodules), a not significant (p = 0.19) difference. In the two cytologically malignant nodules in HT group and 19 in the control group, papillary thyroid carcinoma was diagnosed after thyroidectomy and histopathological examination. US features of nodule echogenicity, structure, margin, and Doppler flow were similar between the two groups. US features of microcalcification and absence of peripheral halo were more prominent in the nodules of the control group (p = 0.002 and p < 0.001, respectively).
On the basis of cytopathological criteria, thyroid nodules in patients with HT are no more likely to be malignant than in those without HT. Many of the US features of benign thyroid nodules are similar in patients with and patients without HT.
To correlate sonographic (US) characteristics and results of fine-needle aspiration biopsy (FNAB) of thyroid nodules in autoimmune thyroiditis (AT) with surgical pathological findings.
Forty AT patients with 40 nodular lesions were analyzed retrospectively. Five sonographic characteristics were recorded for each nodule: diameter, echogenicity, microcalcification, halo sign, and margin. Preoperative sonograms and FNAB results were compared with postoperative histopathological findings.
Twenty-four of the 40 nodules were malignant, including 20 papillary carcinomas, 3 follicular carcinomas, and 1 medullary carcinoma. Of the 16 benign nodules, 8 were nodular hyperplasia, 6 lymphocytic thyroiditis, and 1 each follicular adenoma and Hürthle cell adenoma. The only US parameter that was significant in malignant vs. benign nodules was the presence of poorly defined margins. Based on preoperative cytology, 22 of the 23 malignant nodules were correctly diagnosed, and 10 of the 14 benign nodules were correctly identified. The positive predictive value was 78.6%, and the negative predictive value was 93.7%.
No single US parameter can predict thyroid malignancy in patients with AT. A combination of US and FNAB provides the most sensitive and specific approach available preoperatively.
The purpose of this study is to investigate diagnostic and therapeutic strategies that will enable easy differentiation between minimally invasive follicular carcinoma (MIFC) and widely invasive follicular carcinoma (WIFC). We retrospectively reviewed 234 follicular thyroid carcinoma cases to compare the diagnostic and therapeutic characteristics between the minimally and the widely invasive types. Eighty-nine patients were diagnosed with MIFC (mean age, 39.2 ±14.9 years) and 145 were diagnosed with WIFC (mean age, 49.0 ± 17.7 years). Low diagnostic accuracy from preoperative cytology and frozen sections resulted in 60 patients undergoing subtotal thyroidectomies and 57 cases required a second operation for complete thyroidectomy. Patients in the MIFC group were younger, and had small-sized tumors, lower postoperative thyroglobulin levels, lower recurrent rates and lower cancer mortality rates than those in the WIFC group. Diagnostic accuracy from frozen sections in the WIFC group was relatively better. After a mean follow-up period of 9.0±0.4 years, 41 of the 234 (17.5%) patients with follicular thyroid carcinoma had died due to thyroid cancer. All MIFC patients remained disease-free or had a recurrence-free status. In conclusion, both WIFC and MIFC are difficult to diagnose on the basis of preoperative examinations and frozen sections. Patients diagnosed with MIFC had responded positively to the treatment; however, for patients diagnosed with WIFC to become disease-free, early diagnosis and aggressive surgical therapies in combination with (131)I therapy were required.