Histopathological analysis of papillary thyroid carcinoma detected during ultrasound screening examinations in Fukushima

Thyroid ultrasound screening of young residents in Fukushima Prefecture, Japan, showed a high detection rate of papillary thyroid carcinoma (PTC). Detailed morphological analysis of these tumors was not presented to date. This study sets out to evaluate changes in histopathological and invasive characteristics of Fukushima PTC with time after the nuclear accident of March 2011 in all available cases and in different age subgroups. Histological specimens of 115 PTCs from patients aged 18 years or younger at the time of the Fukushima Dai‐ichi Nuclear Power Plant accident, who underwent surgical resection at Fukushima Medical University during 2012‐2016, were reviewed. Patients were divided into those treated during the first 4 years after the accident (n = 78, shorter‐onset) or later (n = 37, longer‐onset). The whole group and 3 age subgroups: children (aged less than 15 years), adolescents (aged from 15 to less than 19 years), and young adults (aged from 19 years) at surgery were analyzed. No statistically significant time‐related changes in tumor structure or invasiveness were found in the whole group or in age‐matched subgroups. Statistically significant age‐related downtrend was observed for intrathyroid spread in the whole group of patients. The absence of temporal changes in tumor morphological characteristics and tumor invasiveness strongly suggests common etiology of the shorter‐ and longer‐onset Fukushima PTCs, which are unlikely related to the effect of exposure to very low doses of radiation.     

Childhood exposure due to the Chernobyl accident and thyroid cancer risk in contaminated areas of Belarus and Russia.

The thyroid dose due to 131I releases during the Chernobyl accident was reconstructed for children and adolescents in two cities and 2122 settlements in Belarus, and in one city and 607 settlements in the Bryansk district of the Russian Federation. In this area, which covers the two high contamination spots in the two countries following the accident, data on thyroid cancer incidence during the period 1991-1995 were analysed in the light of possible increased thyroid surveillance. Two methods of risk analysis were applied: Poisson regression with results for the single settlements and Monte Carlo (MC) calculations for results in larger areas or sub-populations. Best estimates of both methods agreed well. Poisson regression estimates of 95% confidence intervals (CIs) were considerably smaller than the MC results, which allow for extra-Poisson uncertainties due to reconstructed doses and the background thyroid cancer incidence. The excess absolute risk per unit thyroid dose (EARPD) for the birth cohort 1971-1985 by the MC analysis was 2.1 (95% CI 1.0-4.5) cases per 10(4) person-year Gy. The point estimate is lower by a factor of two than that observed in a pooled study of thyroid cancer risk after external exposures. The excess relative risk per unit thyroid dose was 23 (95% CI 8.6-82) Gy(-1). No significant differences between countries or cities and rural areas were found. In the lowest dose group of the settlements with an average thyroid dose of 0.05 Gy the risk was statistically significantly elevated. Dependencies of risks on age-at-exposure and on gender are consistent with findings after external exposures.     

甲状腺乳头状癌声像图特征探讨

目的：评价甲状腺乳头状癌（papillary thyroid carcinoma,PTC）的声像图特点。方法：回顾性分析34例经手术和病理证实的PTC彩色多普勒超声图像特点。结果：32例（94.1%）低回声,30例（88.2%）结节纵/横≥1,26例（76.5%）伴细微钙化,23例（67.6%）毛剌边缘,29例（85.3%）结节单发,20例（58.8%）边界不清晰,14例（41.2%）侧后方声影,6例（17.6%）检出血流信号,8例（23.5%）颈淋巴结肿大。出现上述异常声像图特征2项以上者占73.5%（25/34）。结论：低回声、微钙化、纵/横≥1、边界、毛剌是PTC具有特征性的超声表现。     

Iodine-131 dose-dependent gene expression: alterations in both normal and tumour thyroid tissues of post-Chernobyl thyroid cancers

Background:

A strong, consistent association between childhood irradiation and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis.

Methods:

We evaluated gene expression in 63 paired RNA specimens from frozen normal and tumour thyroid tissues with individual iodine-131 (I-131) doses (0.008–8.6 Gy, no unirradiated controls) received from Chernobyl fallout during childhood (Ukrainian-American cohort). Approximately half of these randomly selected samples (32 tumour/normal tissue RNA specimens) were hybridised on 64 whole-genome microarrays (Agilent, 4 × 44 K). Associations between I-131 dose and gene expression were assessed separately in normal and tumour tissues using Kruskal−Wallis and linear trend tests. Of 155 genes significantly associated with I-131 after Bonferroni correction and with ⩾2-fold increase per dose category, we selected 95 genes. On the remaining 31 RNA samples these genes were used for validation purposes using qRT−PCR.

Results:

Expression of eight genes (ABCC3, C1orf9, C6orf62, FGFR1OP2, HEY2, NDOR1, STAT3, and UCP3) in normal tissue and six genes (ANKRD46, CD47, HNRNPH1, NDOR1, SCEL, and SERPINA1) in tumour tissue was significantly associated with I-131. PANTHER/DAVID pathway analyses demonstrated significant over-representation of genes coding for nucleic acid binding in normal and tumour tissues, and for p53, EGF, and FGF signalling pathways in tumour tissue.

Conclusion:

The multistep process of radiation carcinogenesis begins in histologically normal thyroid tissue and may involve dose-dependent gene expression changes.     

甲状腺乳头状癌声像图特征探讨

目的:评价甲状腺乳头状癌(papillary thyroid carcinoma,PTC)的声像图特点。方法:回顾性分析34例经手术和病理证实的PTC彩色多普勒超声图像特点。结果:32例(94.1%)低回声,30例(88.2%)结节纵/横≥1,26例(76.5%)伴细微钙化,23例(67.6%)毛剌边缘,29例(85.3%)结节单发,20例(58.8%)边界不清晰,14例(41.2%)侧后方声影,6例(17.6%)检出血流信号,8例(23.5%)颈淋巴结肿大。出现上述异常声像图特征2项以上者占73.5%(25/34)。结论:低回声、微钙化、纵/横≥1、边界、毛剌是PTC具有特征性的超声表现。     

多灶甲状腺乳头状癌的临床特点分析

目的:比较多灶甲状腺乳头状癌(MPTC)与单灶甲状腺乳头状癌(SPTC)的临床和病理特点.方法:回顾性分析我院经手术治疗且病理证实的43例MPTC和78例SPTC患者的临床及病理资料.结果:两组间性别、年龄分段、合并桥本甲状腺炎及结节性甲状腺肿、微小癌比例、病理分期,无统计学差异(P>0.05);MPTC组年龄、腺外浸...     

甲状腺乳头状癌与滤泡状癌的异同探讨

目的　探讨甲状腺乳头状癌与滤泡状癌临床与病理的异同。方法　 42 0例甲状腺癌组织形态学观察、电镜、免疫组化、流式细胞光度术及多参数临床病理分析。结果　甲状腺乳头状癌与滤泡状癌混合型组织结构占绝对优势 ,只是光镜形态不同 ,超微结构观察、免疫组化标记、流式细胞光度测定及临床病理学统计表明两类型未见统计学差异。结论　乳头状癌与滤泡状癌生物学行为相同。     

High prevalence of BRAF mutation in a Brazilian cohort of patients with sporadic papillary thyroid carcinomas

BACKGROUND:

Although several studies undoubtedly demonstrated that BRAF mutation is an important genetic event in the pathogenesis of papillary thyroid carcinoma (PTC), its prognostic significance and correlation with less differentiated states remains unclear. It has been suggested that the discrepancy may be at least partially due to the insufficient number of cases analyzed, epidemiologic factors, and a combination of different variants of PTC included in these studies.

METHODS:

In this context, the prevalence of the BRAF mutation in a Brazilian cohort of PTCs (n = 120) was first assessed and correlated with clinicopathologic features. The BRAF exon 15 mutation was evaluated by direct sequencing. Furthermore, using quantitative polymerase chain reaction, the issue of whether the expression level of the iodide‐metabolizing genes (NIS and TSHR) was correlated with BRAF mutational status was investigated.

RESULTS:

A high prevalence of the BRAF mutation was found in PTC cases (48%). The BRAF mutation was found to be significantly associated with the classic variant of PTC (66%; P < .0001), although it was found in the follicular variant as well (21%). Subtype stratification demonstrated that the BRAF V600E mutation was associated with tumor size, extrathyroid invasion, the presence of lymph node metastasis and risk of disease recurrence, and mortality in patients with the classic variant of PTC. Moreover, the expression levels of NIS and TSHR were remarkably lower in PTCs harboring the BRAF V600E mutation.

CONCLUSIONS:

These findings provide further evidence that BRAF might be associated with a more aggressive phenotype and less differentiated state due to decreased expression of iodide‐metabolizing genes. The search for a BRAF mutation in the current study population appears to be valuable for predicting prognosis and guiding management in patients with PTC. Cancer 2009. © 2009 American Cancer Society.     

A gene expression signature distinguishes normal tissues of sporadic and radiation-induced papillary thyroid carcinomas

Background:Papillary thyroid cancer (PTC) incidence increased dramatically in children after the Chernobyl accident, providing a unique opportunity to investigate the molecular features of radiation-induced thyroid cancer. In contrast to the previous studies that included age-related confounding factors, we investigated mRNA expression in PTC and in the normal contralateral tissues of patients exposed and non-exposed to the Chernobyl fallout, using age- and ethnicity-matched non-irradiated cohorts.Methods:Forty-five patients were analysed by full-genome mRNA microarrays. Twenty-two patients have been exposed to the Chernobyl fallout; 23 others were age-matched and resident in the same regions of Ukraine, but were born after 1 March 1987, that is, were not exposed to (131)I.Results:A gene expression signature of 793 probes corresponding to 403 genes that permitted differentiation between normal tissues from patients exposed and from those who were not exposed to radiation was identified. The differences were confirmed by quantitative RT-PCR. Many deregulated pathways in the exposed normal tissues are related to cell proliferation.Conclusion:Our results suggest that a higher proliferation rate in normal thyroid could be related to radiation-induced cancer either as a predisposition or as a consequence of radiation. The signature allows the identification of radiation-induced thyroid cancers.     

SPON2在甲状腺乳头状癌中的表达及其临床意义

目的：探讨脊椎蛋白2(SPON2)在甲状腺乳头状癌(PTC)中的表达及其临床意义。方法：收集PTC及其癌旁组织新鲜手术标本7例,用实时荧光定量PCR(qPCR)检测PTC及其癌旁组织中SPON2 mRNA的表达情况。并选取2019—2020年间病理科存档PTC石蜡标本68例,采用免疫组织化学SP法检测SPON2蛋白在PTC中的表达情况;并使用Kaplan Meier-Plotter数据库分析SPON2mRNA表达水平与甲状腺癌患者的预后关系。使用GEPIA数据库分析SPON2 mRNA表达水平与甲状腺癌临床分期之间的关系。使用TIMER数据库分析SPON2 mRNA表达水平与甲状腺癌免疫细胞之间的关系。结果：qPCR结果显示,PTC组织SPON2 mRNA相对表达水平为1.705±0.724,明显高于癌旁组织的0.929±0.278,差异具有统计学意义(P=0.036)。免疫组化结果显示,SPON2蛋白表达于细胞质及细胞外基质中,在PTC中的表达显著高于癌旁组织,差异具有统计学意义(P<0.01)。通过GEPIA数据库分析发现,SPON2 m RNA表达差异与甲状腺癌临床分期相关...     

儿童分化型甲状腺乳头状癌的CT特点

目的探讨儿童分化型甲状腺乳头状癌的CT表现特点及诊断价值。方法回顾性分析29例经手术及病理证实的儿童分化型甲状腺乳头状癌的CT影像表现。结果 29例患儿,男10例,女19例,年龄7～14岁.平均11.8岁。CT表现为单发不规则低密度灶3例（10.3%）,表现为多发大小不等、边缘模糊低密度灶19例（65.5%）,表现为腺体对称或不对称性弥漫性增大、密度不均匀减低7例（24.1%）。病灶内出现细颗粒样钙化22例（75.9%）,囊变7例（24.1%）。肿瘤侵犯气管2例（6.9%）,食管3例（10.3%）,局部血管7例（24.1%）28例（96.6%）伴颈部淋巴结转移,分布于Ⅱ区25例（86.2%）,Ⅲ区26例（89.7%）,Ⅳ区26例（89.7%）.Ⅴ区11例（37.9%）,Ⅵ区27例（93.1%）,Ⅶ区12例（41.4%）。转移淋巴结内出现钙化15例（51.74%）,囊变11例（37.9%）。9例（31.0%）出现肺转移。结论儿童甲状腺癌多累及整个腺体,侵袭性强,颈淋巴结转移及肺转移比例高。熟悉儿童甲状腺乳头状癌的CT特点及生物学行为,对手术方案的制定及预后评估有很大的帮助。     

The RET oncogene in papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer, accounting for greater than 80% of cases. Surgical resection, with or without postoperative radioiodine therapy, remains the standard of care for patients with PTC, and the prognosis is generally excellent with appropriate treatment. Despite this, significant numbers of patients will not respond to maximal surgical and medical therapy and ultimately will die from the disease. This mortality reflects an incomplete understanding of the oncogenic mechanisms that initiate, drive, and promote PTC. Nonetheless, significant insights into the pathologic subcellular events underlying PTC have been discovered over the last 2 decades, and this remains an area of significant research interest. Chromosomal rearrangements resulting in the expression of fusion proteins that involve the rearranged during transfection (RET) proto‐oncogene were the first oncogenic events to be identified in PTC. Members of this fusion protein family (the RET/PTC family) appear to play an oncogenic role in approximately 20% of PTCs. Herein, the authors review the current understanding of the clinicopathologic role of RET/PTC fusion proteins in PTC development and progression and the molecular mechanisms by which RET/PTCs exert their oncogenic effects on the thyroid epithelium. Cancer 2015;121:2137–2146. © 2015 American Cancer Society.     

NG及HT合并甲状腺乳头状癌的临床病理分析

目的探讨结节性甲状腺肿(nodular goiter,NG)、桥本氏甲状腺炎(Hashimoto's thyroiditis,HT)合并甲状腺乳头状癌(papillary thyroid carcinoma,PTC)的临床病理特征。方法回顾性分析270例甲状腺乳头状癌患者,筛选NG合并PTC(68例)、HT合并PTC(60例)及单纯PTC(104例)患者将其分成三组,分析其相关临床特征。结果与单纯PTC组比较,NG合并PTC患者中男性比率低、肿瘤直径小、多灶率低、双侧癌比率低、淋巴结转移率低、TGAb表达高和TPOAb表达低等,HT合并PTC患者中男性比率低、肿瘤直径小、多灶率高、双侧癌比率高、淋巴结转移率低、TGAb及TPOAb表达高等临床特征,差异均有统计学意义(均P<0.05)。结论 NG及HT合并甲状腺癌中男性患者较少,肿瘤直径小,淋巴结转移率低,HT合并PTC患者癌灶多灶率高和双侧癌比率较高。     

NA cohort study of thyroid cancer and other thyroid diseases after the Chernobyl accident

BACKGROUND:

The Ukrainian American Cohort Study was established to evaluate the risk of thyroid disorders in a group exposed as children and adolescents to ¹³¹I by the Chernobyl accident (arithmetic mean thyroid dose, 0.79 grays). Individuals are screened by palpation and ultrasound and are referred to surgery according to fine‐needle aspiration biopsy (FNA). However, the accuracy of FNA cytology for detecting histopathologically confirmed malignancy after this level of internal exposure to radioiodines is unknown.

METHODS:

During the first screening cycle (1998‐2000), 13,243 individuals were examined, 356 individuals with thyroid nodules were referred for FNA, 288 individuals completed the procedure, 85 individuals were referred to surgery, 82 individuals underwent surgery, and preoperative cytology was available for review in 78 individuals. Cytologic interpretation for the nodule that resulted in surgical referral was correlated with final pathomorphology; discrepancies were reviewed retrospectively; and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FNA cytology were calculated.

RESULTS:

All 24 cytologic interpretations that were definite for papillary thyroid cancer (PTC) were confirmed histopathologically (PPV, 100%); and, of 11 cytologic interpretations that were suspicious for PTC, 10 were confirmed (PPV, 90.9%). Ten of 41 FNAs that were interpreted as either definite or suspect for follicular neoplasm were confirmed as malignant (PPV, 24.4%), including 2 follicular thyroid cancers and 8 PTCs (all but 1 of the follicular or mixed subtypes). Depending on whether a cytologic interpretation of follicular neoplasm was considered “positive” or “negative,” the sensitivity was 100% and 77.3%, respectively; similarly, the respective specificity was 17.6% and 97.1%, the respective PPV was 61.1% and 97.1%, and the respective NPV was 100% and 76.7%.

CONCLUSIONS:

Among children and adolescents who were exposed to ¹³¹I after the Chernobyl accident and were evaluated 12 to 14 years later, thyroid cytology had a sensitivity and a predictive value similar to those reported in unexposed populations. Cancer (Cancer Cytopathol) 2009. Published 2009 by the American Cancer Society.     

RET rearrangements in post-Chernobyl papillary thyroid carcinomas with a short latency analysed by interphase FISH

Tissue samples from 13 post-Chernobyl childhood thyroid tumours that occurred within a short period of time (4-8 years) after the Chernobyl accident have been investigated by interphase FISH analysis for rearrangements of RET. In all, 77% of cases showed RET/PTC rearrangements and a distinct intratumoural genetic heterogeneity. The data were compared to findings on 32 post-Chernobyl PTCs that occurred after a longer period of time (9-12 years) after the accident. In none of the cases from either group were 100% of cells positive for RET rearrangement. In addition, the pattern of RET-positive cells was different in the two groups (short vs longer latency). A significant clustering of aberrant cells could be detected in the long-latency subgroup, whereas the aberrant cells were more homogeneously distributed among the short-latency tumours. The findings suggest that oligoclonal tumour development occurs in post-Chernobyl PTCs. This pattern of different clones within the tumour appears to become more discrete in cases with longer latencies, suggesting either outgrowth of individual clones or development of later subclones with time.     

Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid: a meta-analysis

BACKGROUND: Numerous studies have investigated the clinical significance of BRAF mutation in papillary thyroid carcinoma (PTC). However, there have been conflicting data on the usefulness of BRAF mutation as a prognostic marker of PTC. To address this controversy, the frequency of the BRAF mutation and the associations between BRAF mutation and clinicopathologic parameters in PTC were evaluated by meta-analysis. METHODS: The relevant published studies were reviewed according to the defined selection criteria. The effect sizes of outcome parameters were estimated by odds ratio or weighted mean difference. RESULTS: The current meta-analysis included 12 studies with a total of 1168 patients. The frequency of the BRAF mutation was 49%. The BRAF mutation was associated with histologic subtype, the presence of extrathyroidal extension, and higher clinical stage, but not with age, sex, race, or tumor size. CONCLUSIONS: The effect of the BRAF mutation on the poor prognosis of PTC patients was evident from the current meta-analysis. The detection of the BRAF mutation may be used as an important prognostic marker of patients with PTC.     

72例甲状腺乳头状微小癌临床病理分析

目的 探讨甲状腺乳头状微小癌(papillary thyroid microcarcinoma,PTM)的临床病理特点.方法 回顾性分析72例PTM患者的临床资料.结果 男性9例,女性63例,男女之比为1∶7,中位年龄分别为49岁和46岁.临床误诊率69.4％ (50/72),采用甲状腺次全切29例,患叶切除术16例,患叶加峡部切除术13例,患叶及峡部及肿大淋巴结清扫术14例(19.4％),淋巴结转移率为85.7％ (12/14),男性女性淋巴结转移率分别为100.0％( 5/5)和77.8％ (7/9)(x2=1.296,P=0.255).多灶15例,单结节57例,淋巴结转移率分别为75.0％ (3/4)和90.0％ (9/10)(x2=0.525,P=0.469).伴有结节性甲状腺肿38例,桥本甲状腺炎2例.病灶长径≥0.5 cm者51例,淋巴结转移率为77.8％ (7/9),＜0.5 cm者21例,淋巴结转移率为100.0％ (5/5)(x2=1.296,P=0.255).≥45岁39例,＜ 45岁33例,淋巴结转移率分别为100.0％ (8/8)和66.7％ (4/6)(x2=3.111,P=0.078).结论 PTM是一种慢性病,临床误诊率较高.在对扪及的肿大淋巴结进行治疗性清扫的PTM病例中,淋巴结转移率极高,但性别、年龄、癌灶数目及大小等因素与PTM淋巴结转移率相关性之间的差异无统计学意义.     

Simultaneous occurrence of medullary carcinoma and papillary carcinoma and papillary carcinoma of the thyroid

We report a case of simultaneous occurrence of medullary carcinoma and papillary carcinoma of the thyroid in the same thyroid gland. Immunoreactivity of calcitonin, carcinoembryonic antigen, neuron specific enolase and thyroglobulin made a sharp distinction between both neoplasms of the thyroid. It appears reasonable to consider that simultaneous occurrence of medullary carcinoma and papillary carcinoma of the thyroid in this case does not have embryological or genetical significance. © 1995 Wiley-Liss, Inc.