Carbonic anhydrase 4 and crystallin alpha-B immunoreactivity may distinguish benign from malignant thyroid nodules in patients with indeterminate thyroid cytology

Background

Thyroid nodules are present in 19%–67% of the population and carry a 5%–10% risk of malignancy. Unfortunately, fine-needle aspiration biopsies are indeterminate in 20%–30% of patients, often necessitating thyroid surgery for diagnosis. Numerous DNA microarray studies including a recently commercialized molecular classifier have helped to better distinguish benign from malignant thyroid nodules. Unfortunately, these assays often require probes for >100 genes, are expensive, and only available at a few laboratories. We sought to validate these DNA microarray assays at the protein level and determine whether simple and widely available immunohistochemical biomarkers alone could distinguish benign from malignant thyroid nodules.

Methods

A tissue microarray (TMA) composed of 26 follicular thyroid carcinomas (FTCs) and 53 follicular adenomas (FAs) from patients with indeterminate thyroid nodules was stained with 17 immunohistochemical biomarkers selected based on prior DNA microarray studies. Antibodies used included galectin 3, growth and differentiation factor 15, protein convertase 2, cluster of differentiation 44 (CD44), glutamic oxaloacetic transaminase 1 (GOT1), trefoil factor 3 (TFF3), Friedreich Ataxia gene (X123), fibroblast growth factor 13 (FGF13), carbonic anhydrase 4 (CA4), crystallin alpha-B (CRYAB), peptidylprolyl isomerase F (PPIF), asparagine synthase (ASNS), sodium channel, non-voltage gated, 1 alpha subunit (SCNN1A), frizzled homolog 1 (FZD1), tyrosine related protein 1 (TYRP1), E cadherin, type 1 (ECAD), and thyroid hormone receptor associated protein 220 (TRAP220). Of note, two of these biomarkers (GOT1 and CD44) are now used in the Afirma classifier assay. We chose to compare specifically FTC versus FA rather than include all histologic categories to create a more uniform immunohistochemical comparison. In addition, we have found that most papillary thyroid carcinoma could often be reasonably distinguished from benign disease by morphological cytology findings alone.

Results

Increased immunoreactivity of CRYAB was associated with thyroid malignancy (c-statistic, 0.644; negative predictive value [NPV], 0.90) and loss of immunoreactivity of CA4 was also associated with malignancy (c-statistic, 0.715; NPV, 0.90) in indeterminate thyroid specimens. The combination of CA4 and CRYAB for discriminating FTC from FA resulted in a better c-statistic of 0.75, sensitivity of 0.76, specificity of 0.59, positive predictive value (PPV) of 0.32, and NPV of 0.91. When comparing widely angioinvasive FTC from FA, the resultant c-statistic improved to 0.84, sensitivity of 0.75, specificity of 0.76, PPV of 0.11, and NPV of 0.99.

Conclusions

Loss of CA4 and increase in CRYAB immunoreactivity distinguish FTC from FA in indeterminate thyroid nodules on a thyroid TMA with an NPV of 91%. Further studies in preoperative patient fine needle aspiration (FNAs) are needed to validate these results.     

Prevalence of malignancy within cytologically indeterminate thyroid nodules

BACKGROUND: The optimal management of cytologically indeterminate thyroid nodules is controversial given the variable malignancy rates reported in this patient population. We examined the prevalence of malignancy within cytologically indeterminate follicular thyroid lesions in an attempt to predict malignancy based on cytologic features. METHODS: Cytopathology reports obtained after fine-needle aspiration biopsy (FNAB) examination of indeterminate follicular thyroid lesions were examined over a 4-year period. The prevalence of malignancy on final histology was determined in 4 indeterminate cytologic categories. RESULTS: A total of 107 records were available (91 women, 16 men). The mean patient age was 45.4 +/- 16 years. Forty-eight patients (45%) underwent surgery and had histopathologic diagnosis, while 57 patients did not have surgery. The prevalence of malignancy in patients who underwent thyroidectomy was 42% (20 of 48). CONCLUSIONS: The high prevalence of malignancy within indeterminate follicular lesions may necessitate thyroidectomy for patients with indeterminate follicular lesions on FNAB examination.     

Prognostic significance of indeterminate lung nodules in renal cell carcinoma

ObjectivesMany patients with renal cell carcinoma (RCC) are found to have lung nodules at the time of diagnosis. The significance of these nodules is unclear. This study sought to determine whether the presence of indeterminate lung nodules affects survival for patients with early-stage RCC.Methods and materialsA retrospective review was performed of patients with stages I to III RCC at an academic hospital who underwent nephrectomy between 2001 and 2006 and had baseline imaging available for review. Presence of lung nodule(s) was determined, along with patient and disease characteristics. The time from diagnosis to last known follow-up, metastasis, and death were determined. The study follow-up period extended to July 2012. Univariate and multivariate Cox proportional hazards models assessed disease-free and overall survival.ResultsOf 548 patients, 240 met the inclusion criteria. Lung nodules were absent in 148 and present in 92 cases. Disease-free survival was associated with the presence of nodules (hazard ratio [HR] = 1.90; 95% CI: 1.04–3.46; P = 0.0362), tumor stage (stage II—HR = 5.61; 95% CI: 2.69–11.72; P<0.001 and stage III—HR = 2.49; 95% CI: 1.21–5.10; P = 0.0129) and tumor grade (HR = 2.43 for grades 3 or 4; 95% CI: 1.31–4.53; P = 0.005). The number and size of nodules were not associated with survival. Overall survival was associated with Charlson comorbidity score (HR = 1.30; 95% CI: 1.15–1.47; P<0.0001) and primary tumor size (HR = 1.29; 95% CI: 1.14–1.46; P<0.0001) but not the presence of lung nodules (HR = 1.73; 95% CI: 0.83–3.60; P = 0.1454).ConclusionsThe presence of indeterminate lung nodules had a negative effect on disease-free survival. Stage and grade were also significant. These findings underscore the importance of baseline imaging and vigilant surveillance of patients in whom nodules are identified.     

Thyroglobulin antibodies as a potential predictive marker of papillary thyroid carcinoma in patients with indeterminate cytology

Backround

We investigated the efficacy of thyroglobulin antibodies (TgAb) in detecting malignancy in indeterminate thyroid nodules and evaluated the possible association between TgAb and autoimmunity in papillary thyroid carcinoma (PTC).

Methods

This retrospective, nonrandomized study included 1,646 patients who had undergone preoperative fine-needle aspiration biopsy to evaluate their thyroid nodules, and then standard total thyroidectomy. Of 194 patients (11.8%) with indeterminate nodules, 61 (31.4%) had PTC and 133 (68.6%) had benign nodules at the final histologic examination.

Results

Univariate analysis showed that multifocality (P = .002), bilaterality (P = .003), lymph-node metastasis (P = .030), and capsule penetration (P = .003) were significantly associated with positive TgAb in patients with indeterminate cytology and histopathologic diagnosis of PTC. The multivariate analysis showed that TgAb positivity (P < .001) and preoperative thyroid-stimulating hormone levels (P = .022) were independent predictive factor for PTC diagnosis in patients with indeterminate cytology.

Conclusions

Preoperative TgAb could be a marker for PTC in patients with indeterminate thyroid nodules, increasing diagnostic accuracy. TgAb positivity could also influence the clinical assessment and subsequent selection of total thyroidectomy.     

超声引导下细针抽吸活检诊断不同大小甲状腺结节

目的探讨甲状腺结节大小对超声引导下细针抽吸活检(US-FNAB)诊断效能的影响。方法选取接受USFNAB且病理证实为甲状腺结节的患者125例(共143个结节),根据结节最大直径(L)分为3组:A组(L≤10mm),B组(10mmL≤15mm),C组(L15mm)。将US-FNAB细胞学诊断结果与病理结果对比,并进行统计学分析。结果143个结节中US-FNAB细胞学诊断阳性结节94个,阴性结节49个;术后病理诊断恶性结节96个,良性结节47个。良、恶性结节大小差异有统计学意义(P0.001)。3组敏感度、特异度差异均有统计学意义(P均0.05),阳性预测值、阴性预测值、假阳性率、假阴性率及准确率差异均无统计学意义(P均0.05)。与A、B组比较,C组敏感度最低(P0.05),A、B组敏感度差异无统计学意义(P0.05)。与B、C组比较,A组特异度最低(P0.05),B、C组特异度差异无统计学意义(P0.05)。结论甲状腺结节大小对US-FNAB诊断的效能无影响。     

Cytohistologic correlation of thyroid nodules

BACKGROUND: Fine-needle aspiration (FNA) is widely used as a diagnostic tool to assess thyroid nodules. This study correlates FNA cytology results with surgical pathologic findings. METHODS: All thyroidectomies performed between 1994 and 2004 were reviewed, identifying 242 patients. Data were obtained for FNA diagnosis, demographics, findings on ultrasound, and histologic findings. RESULTS: Among 89 patients with a carcinoma on FNA, 89% of cases were verified on final histopathology. Of 78 patients with "follicular lesion" on FNA, only 36% of cases were verified to be malignant at surgery. Only 13% of the 75 cases diagnosed as benign, mostly colloid nodules, on FNA were found to have a carcinoma on histopathology. CONCLUSION: A cytologic diagnosis of papillary carcinoma has a highly predictive of thyroid cancer. When dealing with follicular lesions the predictive value of FNA drops considerably. However, we found a 13% false positive result to occur in FNA declared benign lesions.     

甲状腺结节微波热消融治疗的临床进展

甲状腺结节是临床常见疾病,其治疗方式目前主要以外科开放式手术为主,微创治疗一直是临床探索的热点。经超声引导下甲状腺结节微波热消融具有重要的临床意义。本文主要对微波热消融甲状腺结节的治疗指征、临床疗效及常见并发症进行综述。     

热消融术在甲状腺结节微创治疗中的应用进展

目的探讨热消融技术在治疗甲状腺结节中的特点,为临床上选择合适的消融方案提供参考。 方法结合文献分析微波、射频、激光等热消融术的原理,回顾近年来相关技术的临床应用情况,明确各方式的优缺点。 结果虽然众多研究证实热消融在治疗某些甲状腺结节中疗效肯定,但随着临床应用增多其并发症也逐渐被重视,在治疗甲状腺恶性肿瘤及其转移的淋巴结方面尚有其局限性。 结论各种热消融术各有其优势和不足,故在选择热消融治疗时必须严格掌握其适应证。     

超声造影鉴别诊断甲状腺良恶性结节

目的探讨CEUS鉴别诊断甲状腺良恶性结节的价值。方法回顾性分析62例患者67个甲状腺结节的CEUS表现。结果甲状腺恶性结节CEUS多表现为不均匀增强、边界不清,甲状腺良性结节多表现为周边环状强化。根据不均匀强化诊断恶性结节的敏感度为86.84%,特异度为44.83%,阳性预测值为67.35%,阴性预测值为72.22%;边界不清诊断恶性结节的敏感度81.58%,特异度65.52%,阳性预测值75.61%,阴性预测值73.08%;环状强化诊断良性结节的敏感度41.38%,特异度97.37%,阳性预测值92.31%,阴性预测值68.52%。结论 CEUS对鉴别诊断甲状腺良恶性结节具有一定价值。     

超声引导下细针穿刺抽吸活检诊断甲状腺结节

目的探讨超声引导下细针穿刺抽吸活检(US-FNAB)对不同大小甲状腺结节的诊断价值。方法回顾分析在我院接受US-FNAB检查的689例患者736个甲状腺结节,超声测量结节最大径,并将其分为<5mm、5～10mm、>10mm组;对结节US-FNAB细胞学诊断结果与术后病理结果或随访结果进行比较,分析组间差异。结果 736个结节中,细胞学诊断恶性132个,可疑恶性61个,良性476个,不满意44个,不确定23个。经术后病理或临床随访,恶性结节208个,良性结节528个。恶性结节最大径小于良性结节(P<0.001)。5～10mm组结节的细胞学阳性率和实际恶性率均大于<5mm组及>10mm组(P均<0.05)。US-FNAB细胞学诊断甲状腺良恶性结节的敏感度为87.02%(181/208),特异度97.73%(516/528),准确率94.70%(697/736)。不同大小甲状腺结节US-FNAB检查的诊断敏感度、特异度、阳性预测值、阴性预测值及准确率差异均无统计学意义(P均>0.05)。结论 US-FNAB是判断甲状腺结节性质的有效手段,对不同大小结节都有较高诊断价值。     

Treatment of solitary thyroid nodules according to size,preoperative fine-needle aspiration cytology and frozen section: a retrospective single centre study

Background: In order to avoid unnecessary thyroidectomies, it is important to predict the nature of thyroid nodules the more accurately possible. The size of the nodule as a predictive factor for malignancy is very controversial. Another point of debate is the accuracy of preoperative fine-needle aspiration cytology (FNAC) and frozen section (FS). The aim of our study is to correlate the nodule size with the final histological diagnosis and to estimate the accuracy of preoperative FNAC and FS.

Methods: Retrospective study including 387 operated patients with ultrasound-detected solitary thyroid nodules from 01 January 2001 to 31 December 2013. The following data were collected: patient age and sex, nodule size, FNAC, FS and final histology results.

Results: The odds ratio for malignancy within nodules <40?mm was 2.12 (95% CI: 1.104–4.084). The specificity of FNAC was 97.78% and the negative predictive value (NPV) was 97.78% for nodules ≥40?mm and 93.2% and 96.5% for nodules <40?mm, respectively. The observed specificity and NPV of FS ranged from 98% to 100% and from 87.4% to 98%, respectively. When combining FNAC and FS, the specificity and the NPV were 99% and 98%, respectively.

Conclusions: The nodule size is not a predictive factor for thyroid cancer and therefore nodules ≥40?mm should not be routinely resected. A lege artis preparation and performance of FNAC along with an expertise on cytological interpretation can considerably diminish false-negative rate. FS can offer additional accuracy on FNAC results and should, therefore, be a part of patient treatment.     

甲状腺结节良恶性的多因素分析预测

目的 探讨术前常规检查预测甲状腺结节良恶性的可行性及其临床价值.方法 回顾性分析1630例甲状腺结节患者的一般特征、结节的超声特征、实验室检查、核医学表现与最终病理诊断间的关系,筛选高危因素,建立风险预测模型并进行准确率、敏感性和特异性分析.结果 387例囊性为主的甲状腺结节中癌的比例为0.78％;1243例实性为主的甲状腺结节中癌的比例为17.2％,多因素分析显示实性为主的甲状腺结节恶变的高危特征包括:年龄小于40岁,单侧腺叶受累,低回声,边界不清,无囊性变,微钙化,粗钙化,结节最大径≤2 cm,癌风险指数公式为:y=0.80×年龄+0.59×腺叶+0.72×回声+0.82×边界+1.32×实性+1.90×微钙化+0.70×粗钙化+0.71×大小,取风险指数=2.8为临界值,其预测恶性结节的敏感度、特异性和准确率分别为74.4％、80.4％和75.2％. 结论 甲状腺结节病例可通过结合自身一般特征及术前常规检查结果较准确地预测结节的性质,指导手术治疗.     

The impact of synoptic cytology reporting on fine-needle aspiration cytology of thyroid nodules

BACKGROUND: Fine-needle aspiration cytology (FNAC) is integral to the diagnosis and management of patients with thyroid nodules. We introduced synoptic cytology reporting for thyroid nodules in 2004. The aim of this study was to examine the effect of synoptic cytology reporting in our institution. METHODS: A comparative study of two 2-year periods (1 August 2002 to 1 August 2004 and 2 August 2004 to 2 August 2006) before and after the introduction of synoptic reporting was conducted from a prospectively collected database of patients presented with thyroid nodules. The only change during these periods was the format of FNAC reporting. We used the same radiological practice and cytopathology service throughout the study period. All patients are still being followed up. RESULTS: There were a total of 660 patients. Of these, 376 were operated and 284 non-operated. The female to male ratio was 7:1. Comparing the two periods, the overall FNAC sensitivities were 60% versus 79.1%; specificities, 83.7% versus 79.4%; accuracy, 76% versus 79.3%; false-positive result, 16.3% versus 20.6% and false-negative result, 40% versus 20.9%. The non-diagnostic rates were 7.4% versus 3.15%. FNAC prompted surgery in 66.7% versus 100% in carcinoma and 56.4% versus 73.6% in adenoma. A benign FNAC prompted surgery in 15% versus 19.8% of cases. There was no thyroid cancer detected in the current follow up. CONCLUSIONS: Synoptic cytology reporting has resulted in an overall improvement in all measures of the tests. It is a simple and effective tool to use. Synoptic cytology reporting is therefore recommended for all endocrine surgical units.     

经皮激光消融在甲状腺结节治疗中的应用进展

甲状腺结节是最常见的内分泌疾病之一,其中良性结节占多数,目前对于出现明显症状的良性结节可采取手术治疗,但损伤较大。经皮激光消融治疗是近年来出现的一种新的非手术治疗方式,可用于甲状腺良性结节的治疗。本文对经皮激光消融治疗甲状腺良性结节的原理、有效性、适应证、操作步骤、疗效、安全性、前景与展望做一综述。     

The incidence of thyroid cancer by f ine needle aspiration varies by age and gender

Background

Fine needle aspiration (FNA) is the standard to evaluate thyroid nodules for malignancy. The aim of this study was to determine the influence of patient age and gender on the rate of thyroid nodule malignancy by FNA.

Methods

A database of 3981 consecutive patients who underwent thyroid FNA between 2002 and 2009 was reviewed. The percentages of benign, indeterminate, and malignant biopsies based on patient age and gender were determined. Statistical analysis was performed using SPSS (SPSS Inc, Chicago, IL).

Results

Our patient population included 2766 women (mean age ± SD, 52 ± 15.2) and 964 men (mean age ± SD, 59 ± 13.8). Of the 3722 (93.5%) patients with diagnostic FNAs, 196 (5.3%) had malignant FNA cytology. Malignant FNAs were twice as frequent in patients age ≤45 versus those >45 (8.1% versus 4.0%, P < 0.001). Overall, men had more indeterminate (10.2% versus 6.3%, P < 0.001) and malignant (6.7% versus 4.8%, P = 0.034) FNAs than women. Malignant FNAs in men were greatest in patients over age 45 (6.0% versus 3.2%, P = 0.001). The incidence of malignant FNAs for women peaked in their age 30s (10.4%), whereas the incidence of malignant FNAs for men peaked 10 y later in their age 40s (12.1%). Both men and women had the lowest incidence of malignant FNAs in their age 70s (2.3% and 1.9%, respectively).

Conclusions

The typical 5% risk of thyroid nodule malignancy on FNA varies depending on a patient’s age and gender. A patient’s age and gender should, therefore, be considered when counseling someone of his or her risk of thyroid cancer by FNA.     

Needle-localized thoracoscopic resection of indeterminate pulmonary nodules: Impact on management of patients with malignant disease

Background: The efficacy and therapeutic impact of needle-localized thoracoscopic resection (NLTR) was examined in patients with cancer who present with small indeterminate pulmonary nodules (IPNs). Methods: Between December 1991 and August 1992, 30 patients underwent needle localization of 33 IPNs under computed tomography (CT) guidance followed by thoracoscopic resection. All previous attempts to characterize these small pulmonary nodules (mean size 7.9 ± 4.9 mm) had failed. Twenty patients had an established diagnosis of cancer 1 month to 20 years before detection of the lung abnormality, whereas the remaining patients had no prior history of cancer. Results: Histology of NLTR specimens in patients with a previous diagnosis of malignancy included 13 malignant and seven benign lesions. In all patients with cancer, therapeutic decisions were influenced by NLTR results. Thoracoscopic related complications were noted in two patients. Average length of hospital stay for NLTR was 6.7 ± 3.9 days. Conclusion: NLTR in this series has proven to be a safe, well-tolerated, and accurate method for diagnosing and influencing the management of recently identified IPN. NLTR appears warranted for small pulmonary nodules not amenable to less invasive diagnostic modalities.Presented at the 46th Annual Cancer Symposium of The Society of Surgical Oncology, Los Angeles, March 18–21, 1993.     

超声诊断良恶性甲状腺结节的进展

超声检查作为诊断甲状腺结节的首选影像学方法,可快速定位,评估结节大小、形态、内部结构、回声水平及周围淋巴结情况等。弹性成像及CEUS等超声新技术可分别评估甲状腺结节的硬度及血供情况,协助诊断结节性质。本文对超声诊断甲状腺良恶性结节的现状及进展进行综述。     

桥本病合并甲状腺结节的外科治疗

目的 探讨桥本病(HD)并存甲状腺结节的诊治经验.方法 回顾分析我院1995年至2008年手术治疗的,以结节形式为主要症状的187例HD的临床资料.结果 HD并存甲状腺癌21例(11.2%),结节性甲状腺肿50例(26.7%),甲状腺滤泡性腺瘤28例(15%),淋巴瘤3例(1.6%),采取了不同范围的手术方式,术后均服用甲状腺素片.结论 对于HD并存甲状腺结节尤其单结节患者,如临床资料不能除外恶性肿瘤均应积极手术.B超及细胞学穿刺有助于术前诊断,而术中快速病理检查是确诊的有效方法,并指导手术方案的制定.     

长春和上海地区居民甲状腺结节性质的对比分析

目的　探讨长春、上海地区手术切除甲状腺结节的性质差异。方法　回顾性分析长春地区39年间手术切除甲状腺结节标本9216例和上海地区37年间手术切除甲状腺结节标本7018例,比较两地甲状腺囊肿、结节性甲状腺肿、甲状腺瘤、甲状腺癌等疾病的构成差异。结果　长春地区和上海地区甲状腺囊肿占全组资料的比例分别为 1 83%和 8 68%;结节性甲状腺肿为 48 31%和18 62%;甲状腺瘤为39 30%和49 94%;甲状腺癌为10 55%和 22 76%。两组数据间比较差异均有统计学意义。结论　沿海地区和内陆地区以甲状腺结节为表现的甲状腺疾病构成比差异较大。     

超声引导下粗针组织活检在甲状腺结节诊断中的价值

目的 探讨超声引导下粗针组织活检(CNB)对甲状腺结节诊断临床上的应用价值.方法 回顾性分析395例超声引导下甲状腺结节CNB的临床资料,对其中278例行外科手术者CNB及术后石蜡病理学结果进行比较.结果 所有患者均穿刺成功.活检取材满意度为100％.1例出现穿刺后局部血肿,经保守治疗后缓解.共穿刺395例患者,其中278例患者行外科手术,术前CNB病理学结果显示:92例考虑为恶性,其中91例为甲状腺乳头状癌,1例为髓样癌;182例考虑为良性,其中其中1例为甲状旁腺腺瘤,48例为甲状腺腺瘤,133例为结节性甲状腺肿及其他非肿瘤性病变.其中273例穿刺病理学结果与术后石蜡病理学结果相符(90例恶性,183例良性),1例为假阳性,4例不确定病例.故超声引导下CNB对甲状腺结节良、恶性鉴别诊断的准确率、敏感性、特异性、漏诊率和误诊率分别为98.20％ (273/278)、95.79％(91/95)、99.45％(182/183)、4.21％ (4/95)和0.55％ (1/183).结论 超声引导下CNB对甲状腺结节具有很高的鉴别诊断价值,是一种安全、有效的方法.