鉴别甲状腺良恶性结节分子标记物的研究现状

甲状腺结节在临床上十分常见,大致可分为良性结节和甲状腺癌两类,其中良性结节占绝大部分,而甲状腺癌不到5%.不同类型的甲状腺结节性病变治疗原则各不相同,正确判断结节的性质对治疗方案的选择具有十分重要的指导意义.通过确定特异性分子标记物来鉴别甲状腺结节的良、恶性有望为临床处理提供一定的帮助.     

鉴别甲状腺良恶性结节分子标记物的研究现状

甲状腺结节在临床上十分常见,大致可分为良性结节和甲状腺癌两类,其中良性结节占绝大部分,而甲状腺癌不到5%.不同类型的甲状腺结节性病变治疗原则各不相同,正确判断结节的性质对治疗方案的选择具有十分重要的指导意义.通过确定特异性分子标记物来鉴别甲状腺结节的良、恶性有望为临床处理提供一定的帮助.     

甲状腺结节与肿瘤的规范化诊断与治疗

重视甲状腺结节合理与规范的诊断与治疗具有重要意义.甲状腺结节和肿瘤的规范化诊断与治疗包括认真收集和评估病史资料,根据患者的情况选择合理的检查方法和进行规范的治疗,良性甲状腺结节及甲状腺癌治疗后还需要密切随访.     

甲状腺癌与桥本甲状腺炎及其他相关危险因素的研究

目的 探讨甲状腺癌与桥本甲状腺炎及其他相关危险因素的关系.方法 采用回顾性研究方法分析2001年1月-2013年9月于空军总医院经手术治疗的1 141例甲状腺结节患者的临床资料,其中,病理诊断为甲状腺癌270例,甲状腺良性结节871例(甲状腺腺瘤194例,结节性甲状腺肿341例,腺瘤性结节性甲状腺肿336例).比较甲状腺癌患者及甲状腺良性结节患者在桥本甲状腺炎、性别、年龄、病程、结节大小、甲状腺功能等方面的差异,并采用Logistic回归法分析甲状腺癌的危险因素.结果 与甲状腺良性结节患者相比,甲状腺癌患者合并桥本甲状腺炎比例较高(t=20.534,P＜0.01)、患者较年轻(t=0.855,P＜0.01)、结节直径较小(t=-5.927,P＜0.01),促甲状腺激素(TSH)水平(t=2.380,P＜0.05)、甲状腺球蛋白抗体异常率(x2=16.088,P＜0.01)及甲状腺过氧化物酶抗体异常率(x2=7.023,P＜0.01)均较高.Logistic回归分析显示桥本甲状腺炎[优势比(OR)=1.829,95％CI:1.163～2.877,P＜O.01]、年龄≤45岁(OR=1.716,95％CI:1.166～2.528,P＜0.01)、结节直径≤1 cm(OR=4.261,95％ CI:2.467～7.360,P＜0.01)是甲状腺癌的危险因素.结论 桥本甲状腺炎可能是甲状腺癌的危险因素,对于促甲状腺激素、甲状腺球蛋白抗体、甲状腺过氧化物酶抗体水平较高的甲状腺结节患者应高度关注,加强随访.     

儿童甲状腺结节的诊断与治疗

甲状腺结节较少发生于儿童和青少年,但其恶性风险更高,故鉴别其良、恶性非常重要.目前推荐使用的诊断方法主要有甲状腺超声、甲状腺细针穿刺细胞学检查等.儿童甲状腺良性结节的治疗相比成人更为保守,然而对于恶性结节,甲状腺全切术为首选.术后宜密切随访,并正规实施后续治疗.对甲状腺癌术后的患者,需要定期复查放射性碘全身扫描(WBS)、甲状腺球蛋白测定等.左旋甲状腺素的临床效果尚存争议.     

二维超声联合超声造影诊断甲状腺结节120例分析

甲状腺结节是临床上的常见病、多发病,大多数结节属于良性,但随着甲状腺检查技术的进步,甲状腺癌的发病率逐渐升高,使得甲状腺癌成为最常见的内分泌恶性肿瘤,鉴别甲状腺结节的良恶性对治疗方案的选择具有重要意义。目前超声检查是各项检查方法中最准确和最敏感的影像学手段,常规超声对甲状腺结节的良恶性鉴别价值发挥着重要作用,TI-RADS系统是在二维超声的基础上建立起来的标准化工具［2-3］,可评估甲状腺结节的风险。本研究初步探讨甲状腺结节TI-RADS分类联合超声造影对甲状腺结节鉴别诊断的意义。     

甲状腺结节与甲状腺癌的鉴别和最新诊疗方案——中国甲状腺结节和分化型甲状腺癌诊治指南解读

甲状腺结节是一种临床常见病,近年来我国检出率明显增高,甲状腺癌的发病率也呈现增高的趋势。经B超检查发现的甲状腺结节患病率为20％76％,其中甲状腺癌的患病率约为5％～15％。鉴别甲状腺结节的良恶性和评估对周围组织的损害是诊断的重点。收集完整病史有助于甲状腺结节发生甲状腺癌的危险评估。高分辨率超声检查是评估甲状腺结节的首选方法。穿刺活检是评估甲状腺结节良恶性准确性（83％）、特异性（92％）最高的检查。手术治疗、术后^131I治疗和促甲状腺激素（TSH）抑制治疗是甲状腺癌的治疗方法。甲状腺结节和甲状腺癌应视具体情况安排不同时间间隔的随访。与中青年人群相比老年人群甲状腺结节的患病率增高,甲状腺癌的发生率低,治疗原则相同。     

甲状腺结节的射频消融治疗

甲状腺结节是临床常见的甲状腺疾病.射频消融(RFA)治疗能有效地缩小实性甲状腺结节体积,改善结节相关的临床症状.另外,RFA也可用于一些手术风险较高、不愿接受反复手术治疗或复发的甲状腺癌患者.甲状腺RFA治疗的并发症主要包括疼痛、出血、声音改变、皮肤灼伤、甲状腺功能减退症和结节破裂,但绝大部分都能自行恢复.鉴于良好的有效性和安全性,RFA可推荐用于甲状腺结节的临床处理.     

外周血中性粒细胞淋巴细胞比值在甲状腺结节良恶性鉴别诊断中的应用

目的探讨术前外周血中性粒细胞淋巴细胞比值(NLR)在甲状腺结节良恶性鉴别诊断中的应用。方法甲状腺癌患者136例,甲状腺良性结节患者30例,所有病例均经手术病理证实,分析两组术前外周血NLR,并比较甲状腺癌有颈部淋巴结转移者与无淋巴结转移者的NLR。结果甲状腺恶性结节患者NLR高于良性结节组,有颈部淋巴结转移患者NLR高于无淋巴结转移者。结论术前外周血NLR对于甲状腺结节良恶性的鉴别诊断有一定的指导意义,并对甲状腺癌有无颈部淋巴结转移有一定的诊断价值。     

甲状腺疾病血清甲状腺球蛋白检测的临床意义

目的 探讨血清甲状腺球蛋白（Tg）对不同甲状腺疾病的临床诊断意义.方法 916例甲状腺疾病患者,按其临床特征分为Graves病组、原发性甲状腺机能减退组、亚急性甲状腺炎组、良性甲状腺结节组、分化型甲状腺癌组,检测各类甲状腺疾病的血清Tg,比较各组间及分化型甲状腺癌术前、术后血清Tg的水平差异.结果 分化型甲状腺癌组Tg明显高于其他各组（P均＜0.05）,术后6个月分化型甲状腺癌患者Tg水平显著下降（P＜0.05）.结论 血清Tg水平结合临床表现检测有助于甲状腺疾病的诊断及鉴别.     

Long-term risks for thyroid cancer and other neoplasms after exposure to radiation

Radiation-related thyroid cancer continues to be a clinical concern for two reasons: the risks associated with the widespread use of radiation treatments for benign conditions in the middle of the last century persist for decades after exposure; and radiation continues to be an effective component of the treatment of several childhood malignancies. Patients who were irradiated in the head and neck area need to be evaluated for thyroid cancer, benign thyroid nodules, hyperparathyroidism, salivary-gland neoplasms and neural tumors, including acoustic neuromas. Radiation-related thyroid cancers appear to have the same clinical behavior as other thyroid cancers, but many irradiated patients are entering the age range when more aggressive neoplasms occur. In this paper, we review how to approach the clinical management of a patient with a history of radiation exposure in the thyroid area, and how to treat radiation-exposed patients who develop related neoplasms, especially thyroid cancer.     

New guidelines for the management of thyroid nodules and differentiated thyroid cancer

The last 5 years witnessed publication of several multidisciplinary guidelines that address management of benign and malignant thyroid diseases. The primary goal of this review was to excerpt highlights from the most recent 2009 guidelines of the American Thyroid Association that provided recommendations for treating thyroid nodules and differentiated thyroid cancer. There is a systematic algorithm for the evaluation of thyroid nodules based on clinical history, physical examination, measurement of thyroid stimulating hormone (TSH), and neck ultrasound, which has become the preferred radiologic modality for imaging thyroid disease. Radionuclide thyroid scanning is reserved for the evaluation of patients with suppressed TSH levels. Ultrasound-guided fine needle aspiration biopsy (FNAB) is indicated for cytologic assessment of most thyroid nodules >1 cm; additional criteria are specified for FNAB of nodules <1 cm. There is an expanded classification system for reporting thyroid cytologic finding, based on risk of malignancy. Treatment guidelines for thyroid cancer have rapidly evolved. Total thyroidectomy is advocated for initial surgical treatment of differentiated thyroid cancers >1 cm in size. Concurrent therapeutic central and lateral neck dissections remain essential to treat known cervical metastases, but prophylactic central neck dissection is controversial and should be cautiously chosen based on individual patient risk factors. Updates have been made for the use of radioactive iodine ablation and long-term surveillance for thyroid cancer recurrence, where ultrasound imaging is also important. A risk stratification paradigm is proposed to define the chance of recurrence and death from thyroid cancer, and modify treatment plans at various stages of management to the level of risk. Recommendations addressing both benign and malignant thyroid disease topics were graded according to the strength of available and published clinical evidence. Awareness of multidisciplinary recommendations for the treatment of benign and malignant thyroid diseases can enhance the practice of evidence-based medicine and provide practical tools for decision-making relevant to daily clinical encounters.     

Prevalence, clinical and ultrasonographic characteristics of thyroid incidentalomas.

High-resolution ultrasonography (US) has made possible the detection of asymptomatic small thyroid nodules. Thyroid incidentalomas have created a clinical dilemma as to how to properly manage such incidental findings. We investigated the prevalence, the clinical and US characteristics, and optimal diagnostic approach to incidentally detected benign and malignant thyroid nodules < 1.5 cm. Retrospective review was done on 1475 patients who had visited Samsung Medical Center, Soul Korea from January 1999 to December 2000. The prevalence of thyroid incidentalomas was 13.4%. The malignancy rate within thyroid incidentalomas was 28.8%. There were no significant differences in age, nodule size and number, thyroid function test, and Tc99m thyroid scan between benign and malignant incidentalomas. US characteristics of solid echostructure, irregular margin, and calcification showed meaningful diagnostic value in detecting malignancy in thyroid incidentalomas (p < 0.05). Most malignant incidentalomas were low stage. In conclusion, occult thyroid cancers are a fairly common finding. There were no significant differences in clinical and laboratory parameters between benign and malignant thyroid nodules <1.5 cm; however, US findings can be used in the decision of optimal management strategies.     

Growing thyroid nodules with benign histology and RET rearrangement

Some benign thyroid nodules are stationary in size over time while others grow progressively, indicating that there is a broad individual variability within benign nodules. To date, it is very difficult to predict if a benign thyroid nodule will grow in size and which will be its trend over time. While BRAF(V600E) is a highly specific marker of thyroid cancer, RET rearrangements have been disclosed also in non malignant thyroid lesions and their biological significance is debated. We compared the clinical history of three histologically benign thyroid nodules harboring RET rearrangements with that of 6 benign nodules bearing wild type RET. The nodules negative for RET rearrangements were followed for 10 years by ultrasonographic evaluation, showing a slow, constant enlargement. Three patients with benign nodules diagnosed at FNAC, were followed for 11, 9 and 7 years by annual ultrasonographic evaluation. After several years of latency, the nodules had an unexpected and gradual increase in their dimensions, reaching a large final size. A second FNAC confirmed the previous cytologic diagnosis of benign lesion. Because of the increasing size of the nodules, the patients were advised to surgery. Before undergoing thyroidectomy, we performed molecular diagnostic tests that revealed the absence of BRAF(V600E) and the presence of RET/PTC-1 in one nodule and RET/PTC-3 in the two others. Despite the presence of this oncogene, the samples were histologically classified as benign hyperplastic nodules. These findings lead us to speculate that histologically benign hyperplastic thyroid nodules containing RET rearrangements might represent a subgroup of nodules with a rapid size increase.     

RET/PTC rearrangement in benign and malignant thyroid diseases: a clinical standpoint

Cytological examination of fine needle aspiration biopsy is the primary means for distinguishing benign from malignant nodules. However, as inconclusive cytology is very frequent, the introduction of molecular markers in the preoperative diagnosis of thyroid nodules has been proposed in recent years. In this article, we review the clinical implications of preoperative detection of rearrangements of the RET gene (RET/papillary thyroid carcinoma (PTC)) in thyroid nodules. The prevalence of RET/PTC in PTC depends on the histological subtypes, geographical factors, radiation exposure, and detection method. Initially, RET/PTC was considered an exclusive PTC hallmark and later it was also found sporadically in benign thyroid lesions. More recently, the very sensitive detection methods, interphase fluorescence in situ hybridization (FISH) and Southern blot on RT-PCR amplicons, demonstrated that the oligoclonal occurrence of RET rearrangement in benign thyroid lesions is not a rare event and suggested that it could be associated with a faster enlargement in benign nodules. For this reason, RET/PTC cannot be considered as an absolute marker of PTC, and its diagnostic application must be limited to assays able to distinguish between clonal and oligoclonal expression. Detection of RET/PTC by quantitative assays will be useful for diagnostic purposes in cytology specimens when a precise cutoff will be fixed in a clinical setting. Until that time, less sensitive RET/PTC detection methods and FISH analysis remain the most appropriate means to refine inconclusive cytology. Future studies with a long follow-up will further clarify the clinical significance of low level of RET rearrangements in benign nodules.     

Usefulness of repeated fine-needle cytology in the follow-up of non-operated thyroid nodules

OBJECTIVE: The usefulness of repeated fine-needle cytology (FNC) in thyroid nodules with benign cytology remains unknown. We analyzed the relevance of repeated FNC to detect suspicious or malignant (S/M) cytologies and carcinomas. DESIGN: A retrospective study (1983-2004) was conducted in our endocrinology department. METHODS: We reviewed the reports of 895 adequate FNC performed in 298 patients (298 nodules) during a mean follow-up of 5 years. We compared the nodules with at least one suspicious or malignant FNC (S/M nodules) with nodules with repeatedly benign (RB) FNC (RB nodules). RESULTS: Among the nodules with initial benign cytology, we found 35 nodules with one or more later suspicious or malignant results. The interval between the first FNC and the first S/M FNC was 2.9 years. The probability for a nodule to have a repeated benign FNC decreases with time and with the number of FNC. We did not find any clinical or ultrasonographic characteristics related to an S/M cytology. Seven cancers were detected by the second or the third FNC with S/M results. The proportion of cancers among S/M nodules was similar when S/M cytology appears during the first, the second, or the third FNC. CONCLUSIONS: We suggest to repeat FNC up to three adequate samples in the follow-up of thyroid nodules so as not to miss the presence of malignant neoplasm.     

积极推进我国甲状腺结节和肿瘤诊治的规范化

简要介绍了甲状腺结节和甲状腺癌的发病情况及临床评估和处理的当前观点.分析了我国目前存在的问题并提出了解决途径.甲状腺细针穿刺活检开展不够,缺乏专门甲状腺细胞病理医生及相关学科之间缺乏交流是导致我国甲状腺结节和肿瘤诊治工作滞后的主要原因.     

Reliability of fine-needle aspiration in patients with familial nonmedullary thyroid cancer.

In this case-control study we describe how often thyroid cancers and occult cancers are diagnosed or not diagnosed by fine-needle aspiration (FNA) in patients with thyroid nodules and a family history of nonmedullary thyroid cancers (FNMTC). Our hypothesis is that patients with thyroid nodules and a family history of FNMTC seem to be similar to patients with thyroid nodules and a history of exposure to low-dose therapeutic radiation. Both have been reported to have multifocal thyroid neoplasms and malignant tumors are common. Cytological examination may therefore be less accurate. From 1979 to 1996, 27 patients from 24 families with FNMTC were examined histologically after a preoperative cytological examination in all of them. A positive cytology examination was defined when biopsy documented thyroid cancer. It was interpreted as a false-negative study when a benign diagnosis was made and thyroid cancer was present anywhere within the thyroid, including in areas sampled or not sampled by FNA and not palpable preoperatively. A randomized control group, matched for age and gender, contained 27 patients with papillary thyroid cancer without familial disease. In our study group, 25 patients were treated with total thyroidectomy, including 7 with neck dissection, and 2 by thyroid lobectomy. At final histological examination 17 of 27 patients (63%) in this study group had multiple nodules and 25 of 27 (92.6%) had thyroid cancer. Thyroid cancer was diagnosed by FNA in 22 of 25 patients (88%), with 3 (12%) false-negative biopsies due to sampling errors (thyroid cancer not in the index nodule), versus 1 (3.7%) false-negative biopsy in the control group. Two patients in the study group with benign nodules were accurately diagnosed. In patients with false-negative biopsies and a history of FNMTC, the cancer was situated in one or more small nodules. Only one cancer was occult (< 1.0 cm). One-third of the patients in our study group (33%) had a history of radiation; 44% of the irradiated group had a single nodule; 56% had multiple nodules. In the control group, 9 of 27 patients (33%) also had a history of radiation; 33% of the irradiated group had a single nodule, 67% had multiple nodules. In conclusion, the reliability of FNA in patients with FNMTC appears to be less accurate than it is for other patients because of the high incidence of multifocal thyroid cancer and coexistence of benign nodules. Patients with thyroid nodules and a family history of thyroid cancer are more likely to have thyroid cancer and because they also have more coexistent benign nodules, they must be followed closely or treated with total or near-total thyroidectomy.