Clinical significance of extrathyroidal extension according to primary tumor size in papillary thyroid carcinoma

Background

Extrathyroidal extension (ETE) is a risk factor for poor papillary thyroid carcinoma (PTC) outcomes. However, the clinical significance of ETE according to primary tumor size has not been well-established. The purpose of this study was to compare differences in clinical outcomes, according to the presence and extent of ETE, between different primary tumor size groups.

Plk1和p27在甲状腺乳头状癌中的表达及预后意义

目的:探讨Plk1和p27在甲状腺乳头状癌中的表达及与甲状腺乳头状癌预后的关系。方法:采用免疫组织化学技术检测Plk1和p27在甲状腺乳头状癌中的表达情况。结果:甲状腺乳头状癌中Plk1的阳性表达率明显高于正常甲状腺组织（P<0.05）。Plk1在微灶癌（直径≤1cm）中的阳性表达率明显高于在癌灶直径>1cm的甲状腺乳头状癌(P<0.05)。甲状腺乳头状癌中p27阳性表达率（44.12%）明显低于正常甲状腺组织（80.00%,P<0.05）。Plk1和 p27表达与包膜浸润、淋巴结转移情况相关。结论:Plk1在早期甲状腺乳头状癌的发生、发展中起重要作用,联合检测Plk1和p27 有助于甲状腺乳头状癌的诊断及预后评估。     

超声联合肿瘤标志物检测对甲状腺乳头状癌的诊断价值

目的:探讨超声联合肿瘤标志物检测对甲状腺乳头状癌（papillary thyroid carcinoma,PTC）的诊断价值。方法:选择PTC患者62例并定义为观察组,结节性甲状腺肿45例并定义为对照组。分析超声诊断及肿瘤标志物单独诊断PTC的敏感度和特异度。分析肿瘤标志物单独诊断PTC特异度最高的标志物联合超声诊断PTC的敏感性和特异性。结果:超声诊断PTC的敏感性为98.39%,特异性为77.78%;CK19单独诊断的敏感性为70.97%,特异性为95.56%,Galectin-3的敏感性为79.03%,特异性为86.67%;超声联合CK19诊断的敏感性为93.55%,特异性为91.11%。结论:超声诊断联合CK19在PTC疾病诊断中具有一定的价值,可作为诊断PTC疾病的指标之一。     

Lymph node dissection in papillary or follicular thyroid carcinoma

BACKGROUND: Prospective randomized studies aimed at evaluating the different therapeutic protocols for the treatment of papillary or follicular carcinoma are lacking at the moment. Although total thyroidectomy is widely accepted, indication to locoregional lymphadenectomy is strongly debated. MATERIALS AND METHODS: Fifty-four patients with papillary or follicular thyroid carcinoma (45 papillary and 9 follicular) underwent functional evaluation of the gland before intervention, FNAB included Surgical management was carried out as follows: 41 total thyroidectomy, 6 lobectomy with further totalization in 5, 6 total thyroidectomy plus central compartment lymphadenectomy and 1 left laterocervical lymphadenectomy (papillary carcinoma, treated elsewhere through total thyroidectomy plus central and right laterocervical lymphadenectomy). All operated patients were submitted to whole body scintigraphy and treated thereafter by radiometabolic therapy and chronic hormone suppressive therapy. RESULTS: Fifty-one patients are currently alive, 3 died from non-related causes; surgical complications included 1 permanent impairment of inferior laryngeal nerve function and 1 case of hypoparathyroidism. The follow-up was from 1 to 139 months. DISCUSSION: The optimal treatment of lymph node metastases, especially for papillary carcinomas, has not yet been defined. Two trends are evident concerning lymphadenectomy: the first one suggests routine lymphadenectomy, the second supports lymphadenectomy by necessity. In follicular carcinoma lymphadenectomy is recommended only in the presence of clinical evidence of lymph node involvement. Occult differentiated carcinoma does not require any further treatment of lymph nodes. CONCLUSION: Considering the high efficacy of radiometabolic treatment after total thyroidectomy combined with chronic TSH inhibition through L-tyrosine administration, lymphadenectomy is suggested only by necessity.     

Parental cancer and risk of papillary and follicular thyroid carcinoma.

In a population-based case-control study in the Uppsala-Orebro Health Care Region of Sweden, the histories of cancer among parents of 517 histologically confirmed cases of papillary and follicular carcinoma and of a similar number of sex- and age-matched controls were compared. The parental history of cancer was compiled through information from death certificates and from the nationwide Cancer Register. The incidence of malignancies in a cohort of parents of cases of thyroid cancer was also compared with the incidence in the whole Swedish population. A maternal history of cancer was more common among women with follicular carcinoma than among their controls (OR 2.11, 95% CI 0.96-4.67). Parents of probands with papillary carcinoma had an increased risk of thyroid cancer (OR 4.25, 95% CI 1.16-10.89), and mothers of probands with follicular carcinoma had an increased risk of stomach cancer (OR 3.65, 95% CI 0.99-9.35) compared with the general population. Cancer of the lung, breast, and pancreas were less common than in the general population. Familial cases of thyroid cancer were not limited to the papillary type. An inheritable pattern of carcinogenesis is possible for certain differentiated non-medullary thyroid cancers, but shared environmental exposures may also explain the parent-child associations of cancer in this study.     

甲状腺乳头状癌预后相关因素研究进展

甲状腺乳头状癌的发病率在全球范围内呈上升趋势,因为预后良好,这些患者一度被认为是低风险的。然而,局部晚期以及转移性甲状腺乳头状癌的发病率也在上升,与之相关的死亡率也在增加。因此,如何对甲状腺乳头状癌患者进行预后评估是当下研究的热点,本文将对现阶段甲状腺乳头状癌预后相关因素的研究进行综述。     

甲状腺乳头状癌潜在预后生物标志物的识别北大核心

目的:探讨甲状腺乳头状癌的潜在发病机制、治疗靶点及预后生物标志物。方法:使用加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA)基于来自Gene Expression Omnibus数据库的数据集GSE27155和GSE58545构建共表达网络,从而识别与甲状腺乳头状癌密切相关的模块和基因。使用来自于Gene Expression Profiling Interactive Analysis的数据来进行验证。结果:本研究发现棕色模块表明与该疾病密切相关,且该模块中的基因被富集到Ras信号通路、MAPK信号通路及Wnt信号通路等(P<0.05)。基于生存分析发现:4个枢纽基因LMOD1、GHR、GPM6A和ZMAT4与患者预后相关。来自GEPIA的数据显示枢纽基因的差异表达具有显著性意义。结论:本次研究证实棕色模块的枢纽基因LMOD1、GHR、GPM6A和ZMAT4可能为甲状腺乳头状癌潜在发病机制提供了新的切入点,对该疾病临床治疗提供新的见解,对于完善个体化治疗提供一定的帮助。     

Differential miRNA expression profiles in variants of papillary thyroid carcinoma and encapsulated follicular thyroid tumours

Background:

Recent studies showed a significant upregulation of distinct microRNAs (miRNAs) in papillary thyroid carcinoma (PTC). The objective of this study was to explore whether this upregulation could also be assigned to distinct histomorphological variants of PTC, especially the follicular variant and other encapsulated follicular thyroid tumours.

Methods:

We used total RNA of 113 formalin-fixed paraffin-embedded tissues of 50 PTCs ((10 conventional type (PTC-CT), 10 tall cell variants (PTC-TCVs), 30 follicular variants (PTC-FVs)), 10 follicular adenomas (FAs), 10 multinodular goitres (MNGs), 21 follicular thyroid carcinomas and 22 well-differentiated tumours of unknown malignant potential (WDT-UMP) to analyse the miRNA expression pattern of five selected miRNAs (146b, 181b, 21, 221 and 222) using RT–PCR TaqMan miRNA assay to explore the diagnostic utility of this method.

Results:

The mean values of the expression pattern of all miRNAS in PTCs show a statistically significant difference from those in MNG and FA with fold changes up to 90 for miRNA 146b, P<0.001. No differences in expression pattern could be showed between MNG and FA. The PTC-FVs differ significantly from FA in all five miRNAS, from MNG in three and from WDT-UMP in one miRNA with fold changes between 1.7 and 21.2, but failed to be of diagnostic value regarding individual cases with substantial overlaps.

Conclusion:

We conclude that analysis of a set of five selected miRNAS distinguish common variants of PTC from FA/MNG but failed to be a useful diagnostic method in individual and doubtful cases, especially in the differential diagnosis of encapsulated follicular thyroid tumours.     

Prognostic value of oncoprotein expressions in thyroid papillary carcinoma

The aim of this study was to evaluate the expressions of oncoproteins and to correlate the results with clinicopathologic parameters in papillary thyroid carcinoma (PTC). Papillary thyroid cancer (PTC) is the most common form and accounts for about 80% of all thyroid cancers. Although PTC generally has a good prognosis, some patients suffer from local recurrence and/or distant metastasis. Oncogenes have reported to be related not only in carcinogenesis but also in tumor prognosis, tumor type, differentiation and site of tumor in epithelial malignant tumors such as thyroid, breast, ovarian, and stomach cancer. This study was planned retrospectively and was performed in 87 patients (47 PTC, 40 benign lesions). The data of clinicopathologic parameters and tissue samples were collected from the archives. Sections stained with H&E were evaluated for each case and after confirming the diagnosis of PTC, oncoprotein expressions were determined by immunohistochemical analysis. The differences of oncoprotein expressions in PTC compared with control group were statistically significant. Cyclin D1 and p53 expressions were significantly increased in PTC. The expressions of bcl-2 and c-erbB-2 in PTC were found as increased, but the correlation between these proteins and poor prognostic parameters were not significant. We suggest that increased expressions of cyclin D1 and p53 could be used as prognostic factors in patients with PTC.     

Pure versus follicular variant of papillary thyroid carcinoma: clinical features,prognostic factors,treatment, and survival

BACKGROUND: The follicular variant of papillary thyroid carcinoma (FVPTC) is a common subtype of papillary thyroid carcinoma. Few studies have compared the clinical behavior and treatment outcome of patients with FVPTC with the outcome of patients with pure papillary carcinoma (PTC). A retrospective study was performed to identify the influence of FVPTC compared with PTC on therapeutic variables, prognostic variables, and survival. METHODS: A clinicopathologic analysis of 243 patients with papillary carcinoma was performed. One hundred forty-three tumors were PTC, and 100 tumors were FVPTC. The following variables were evaluated: age at diagnosis, tumor size, stage of tumor, treatment, capsular invasion, and survival. RESULTS: The median follow-up was 11.5 years. The median age was 43 years in the PTC group and 44 years in the FVPTC group. The median tumor size, disease stage, and type of initial surgery and iodine 131 ablation were similar. More patients had capsular invasion by the tumor and less metastases to cervical lymph nodes in the FVPTC group. The actuarial survival of patients age < 40 years was higher compared with the survival of patients age > 50 years in both groups. The 21-year overall actuarial survival was 82% in patients with PTC and 86% in patients with FVPTC (P value not significant). CONCLUSIONS: The pathologic and clinical behaviors of PTC and FVPTC were comparable. Prognostic factors, treatment, and survival also were similar. Patients in both groups must be treated identically.     

Prognostic indices for tumor relapse and tumor mortality in follicular thyroid carcinoma

To establish an objective basis for therapeutic decisions and follow-up programs in patients with follicular thyroid cancer, the authors developed a prognostic scoring system. The prognostic impact of nine clinical, histologic, and therapeutic parameters was quantified retrospectively based on a multivariate analysis covering 149 patients. The relative relapse risk in follicular thyroid cancer (RR) was 6.8-fold increased in the presence of a moderate when compared with a high degree of histologic tumor differentiation. The RR rose with increasing age of the patient at time of tumor diagnosis by a factor of 1.8 per 20 years. The RR was reduced by a factor of 4.3 after the performance of a neck dissection and by a factor of 2.3 after percutaneous radiation therapy of the neck. The relative mortality risk in follicular thyroid cancer (RM) rose in the absence of a tumor capsule by a factor of 10, in the presence of a moderate compared with a high degree of histologic tumor differentiation by a factor of 5.9, in the presence of distant metastases by a factor of 3.2, and with increasing age of the patient at the time of tumor diagnosis by a factor of 2.2 per 20 years. From these data prognostic indices denoting the individual risk for tumor relapse (IRR index) and tumor mortality (IMR index) were calculated. The indices categorize patients into low-risk, medium-risk, or high-risk groups with regard to tumor relapse and tumor-related death. Consequently, the IRR and IMR indices contribute to select patients with follicular thyroid cancer who need an aggressive form of treatment and an intensive follow-up program. The indices may also be used for risk stratification in prospective therapy trials.     

119例甲状腺滤泡状癌患者的治疗及预后因素分析

目的 探讨甲状腺滤泡状癌的最佳治疗方案以及影响患者预后的相关因素.方法 回顾性分析119例甲状腺滤泡状癌患者的临床资料.采用Kaplan-Meier法计算生存率,影响患者预后的单因素分析采用Log rank检验,多因素分析采用Cox回归模型.结果 119例甲状腺滤泡状癌患者的5和10年总生存率分别为81.1％和66.7％,就诊时患者的远处转移率为16.0％,3、5、10年累积远处转移率分别为27.4％、29.6％和35.9％.术后行131Ⅰ治疗16例,治疗效果满意9例.单因素分析结果显示,年龄、肿瘤直径、肿瘤生长方式、临床分期和脉管瘤栓均与患者的远处转移情况有关(均P＜0.05);年龄、肿瘤直径、肿瘤生长方式、pN分期、M分期、临床分期、有无脉管瘤栓和肿瘤切除程度均与患者预后有关(均P ＜0.05).Cox回归分析结果显示,年龄是影响患者远处转移的独立危险因素(P＜0.05);肿瘤直径、有无脉管瘤栓、肿瘤切除程度及有无远处转移是影响患者生存的独立因素(均P＜0.05).结论 甲状腺滤泡状癌常呈弥漫性生长,伴有脉管瘤栓,预后相对不良.手术彻底切除是提高局部控制率和改善患者预后的关键.对于年龄≥45岁患者,建议行全甲状腺切除联合131Ⅰ治疗等.     

Prognostic value of E-cadherin expression in thyroid follicular carcinoma.

AIMS: To evaluate the expression of E-cadherin, its association with various clinicopathological features and its possible relation with distant metastasis-free survival (DMFS) in follicular carcinoma of the thyroid. METHODS: E-cadherin expression was assessed immunohistochemically in sections from paraffin embedded tissues in a group of 54 patients with follicular carcinoma and its variants who were followed for a median of 7.25 years. RESULTS: Reduced E-cadherin expression, defined as <90% of cells showing membrane positivity, was found in 15 tumours and was significantly associated with widely invasive growth, insular morphology and lesser degree of differentiation, but was not related to patient sex and age or tumour size. In univariate analysis, DMFS was significantly worse in male patients (P<0.03), widely invasive tumours (P=0.0002), moderately/poorly differentiated tumours (P<0.05) and tumours showing reduced E-cadherin expression (P=0.0001). In multivariate analysis, the degree of invasiveness and E-cadherin expression were the only independent prognostic factors. Among widely invasive cases, those with reduced E-cadherin expression had significantly worse DMFS than those with preserved expression. CONCLUSIONS: Our findings suggest that E-cadherin expression could be used as a prognostic marker in widely invasive follicular carcinomas of the thyroid. Larger studies are needed to assess its prognostic value in the group of minimally invasive carcinomas.     

Increased incidence of papillary thyroid microcarcinoma with decreased tumor size of thyroid cancer

The prevalence of papillary thyroid microcarcinoma (PTMC) in thyroid cancer varies from 20.0% to 42.8% with a mean of 30.0%. Most of these patients have benign clinical courses and receive less aggressive therapeutic procedures in most medical centers. This study retrospectively reviewed 30 years data in one institute and compared it with recent publications to illustrate change in trends and influence of PTMC. Incidental PTMC is usually diagnosed as a postoperative microcarcinoma following thyroidectomy for presumably benign thyroid lesions. Subtotal thyroidectomy or lobectomy without radioactive iodide treatment is sufficient to treat incidental PTMC. In contrast, aggressive surgical treatment with ¹³¹I therapy is indicated for non-incidental PTMC. Those with PTMC in the absence of extra-thyroid invasion diagnosed by postoperative permanent section received follow-up if they had initially received subtotal thyroidectomy. In long-term follow-up studies, cancer-specific mortality for PTMC ranged from 0% to 4%. Most of the mortality cases had distant metastasis at the time of surgery. The clinical course and therapeutic strategies for the non-incidental PTMC patients depend on the TNM stage at the time of diagnosis. One-third of PTMC with clinically aggressive behavior cannot be treated as indolent disease. Invasive tumor markers or larger tumor size are useful to predict tumor recurrence or distant metastasis for PTMC.     

Neuroendocrine differentiation in follicle-cell thyroid carcinoma: correlation to prognostic factors in papillary carcinoma

The presence of NE-differentiation in the follicle-cell thyroid carcinoma has been investigated by immunohistochemical detection of chromogranin A in the neoplastic cells. It has been found that NE-differentiation was present in a significant percentage in the papillary Ca alone (46.60%) whereas all Huerthle-cell neoplasms and the large majority of follicular and undifferentiated carcinomas showed non reactivity for Chromogranin A. Moreover, we have correlated the presence of NE-differentiation to well known prognostic factors in papillary Ca. We found a statistically significant correlation between the neuroendocrine differentiation and some unfavourable factors such as old age of the patient, size of the tumor, invasion of thyroid capsule and lymphnode involvement. We suggested that NE-differentiation could be considered as an index of poor prognosis.     

Potential diagnostic utility of CD56 and claudin-1 in papillary thyroid carcinoma and solitary follicular thyroid nodules

Background and AimThe pathological diagnosis of papillary thyroid carcinoma (PTC) is usually easily achieved. However distinguishing the follicular variant of papillary carcinoma (FVPC) from other follicular thyroid lesions is an area of controversy. In this study we investigated the role of CD56 and claudin-1 in discriminating the FVPCs from other solitary follicular patterned nodules. We also evaluated the application of these two markers in reclassifying the controversial cases of the well differentiated tumors of unknown malignant potential (WDTs-UMP).Materials and methodsThe immunohistochemical expression of CD56 and claudin-1 was evaluated in 86 samples of thyroid lesions together with 10 samples of normal thyroid tissue. Thyroid lesions included: 29 PTCs [classic papillary carcinoma (n = 13) and FVPC (n = 16)], 47 solitary follicular patterned nodules [follicular adenomas (n = 12), hyperplastic nodules (n = 32) and follicular tumor of unknown malignant potential (n = 3)] and 10 WDTs-UMP.ResultsThe statistical analysis showed significantly different expressions of each of CD56 and claudin-1 in the FVPCs versus other solitary follicular patterned nodules. Claudin-1 sensitivity (100%) was higher than CD56 sensitivity (81.3%). However claudin-1 specificity (80.9%) was < CD56 specificity (89.4%). The combined use of CD56 and claudin-1(claudin-1+/CD56?) showed specificity (100%), positive predictive value (100%) and sensitivity (81.3%) in the differentiation between the FVPCs and other follicular nodules. In the light of this statistical outcome, 5/10 cases of WDTs-UMP expressing the (claudin-1+/CD56?) panel could be rediagnosed as PTC.ConclusionCombined utility of CD56 and claudin-1 is helpful in diagnosing the FVPC and its differentiation from other follicular patterned nodules. Application of these two markers may greatly aid in the reevaluation of the WDTs-UMP and interpretation of their expected behavior.     

Multicentric papillary and follicular carcinomas of the thyroid

A 63-year-old female, complaining of a swelling in the neck, was diagnosed as having a thyroid carcinoma. Thus, a subtotal thyroidectomy was performed, leaving a part of the right lobe. Two thyroid carcinomas were found in the left lobe, and one carcinoma in the right lobe with a right cervical lymph nodal involvement. Each carcinoma was small and encapsulated by thick fibrous tissue, but there was no continuity among them. The three carcinomas were regarded as being multicentric in origin, and not an intraglandular metastasis.