An EcoRI RFLP in the 5′ region of the human NF1 gene

Von Recklinghausen neurofibromatosis or type l neurofibromatosis (NF1), is one of the most common autosomal dominant disorders. NF1 is characterized by neurofibromas, café-au-lait spots and Lisch nodules of the iris. The NF1 gene is located in 17q11.2. The restriction fragment length polymorphism reported here will be useful in linkage analysis in NF1 families.     

Pigment cell-related manifestations in neurofibromatosis type 1: an overview

Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder, affecting approximately 1 in 3500 individuals. The most commonly seen tumors in NF1 patients are the (sub)cutaneous neurofibromas. However, individuals with NF1 typically present in childhood with well-defined pigmentary defects, including cafe-au-lait macules (CALMs), intertriginous freckling and iris Lisch nodules. NF1 is considered a neurocristopathy, primarily affecting tissues derived from the neural crest. Since the pigment producing melanocyte originates in the neural crest, the presence of (hyper)pigmentary lesions in the NF1 phenotype because of changes in melanocyte cell growth and differentiation is to be expected. We want to discuss the pigmentary cutaneous manifestations of NF1 represented by CALMs and intertriginous freckles and the pigmentary non-cutaneous manifestations represented by iris Lisch nodules. Several hypotheses have been suggested in explaining the poorly understood etiopathogenesis of CALMs. Whether other pigmentary manifestations might share similar etiopathogenic mechanisms remains obscure. Additional attention will be drawn to a readily seen phenomenon in NF1: hyperpigmentation overlying (plexiform) neurofibromas, which could suggest common etiopathogenetic-environmental cues or mechanisms underlying CALMs and neurofibromas. Finally, we want to address the relationship between malignant melanoma and NF1.     

Klinik und Genetik der Neurofibromatose Typ 1

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1 gene located on chromosome 17q11.2. NF1 is fully penetrant, meaning that every individual carrying the mutation exhibits symptoms of the disease, although with some considerably variable expressivity. NF1 is characterised by the eponymous neurofibromas, which are benign Schwann cell tumours. Among the other main characteristic features of NF1 are pigmentary anomalies such as café-au-lait spots, axillary or inguinal freckling, and Lisch nodules. NF1 is a member of the class of hereditary cancer syndromes, and patients with NF1 are at increased risk of developing specific NF1-associated tumours. These tumours are caused by the biallelic inactivation of the NF1 tumour suppressor gene, resulting in aberrant Ras regulation. Over the last few years, significant progress has been made in identifying and managing the clinical symptoms of NF1 as well as in developing novel therapeutic approaches.     

Pigment cell‐related manifestations in neurofibromatosis type 1: an overview

Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder, affecting approximately 1 in 3500 individuals. The most commonly seen tumors in NF1 patients are the (sub)cutaneous neurofibromas. However, individuals with NF1 typically present in childhood with well‐defined pigmentary defects, including café‐au‐lait macules (CALMs), intertriginous freckling and iris Lisch nodules. NF1 is considered a neurocristopathy, primarily affecting tissues derived from the neural crest. Since the pigment producing melanocyte originates in the neural crest, the presence of (hyper)pigmentary lesions in the NF1 phenotype because of changes in melanocyte cell growth and differentiation is to be expected. We want to discuss the pigmentary cutaneous manifestations of NF1 represented by CALMs and intertriginous freckles and the pigmentary non‐cutaneous manifestations represented by iris Lisch nodules. Several hypotheses have been suggested in explaining the poorly understood etiopathogenesis of CALMs. Whether other pigmentary manifestations might share similar etiopathogenic mechanisms remains obscure. Additional attention will be drawn to a readily seen phenomenon in NF1: hyperpigmentation overlying (plexiform) neurofibromas, which could suggest common etiopathogenetic‐environmental cues or mechanisms underlying CALMs and neurofibromas. Finally, we want to address the relationship between malignant melanoma and NF1.     

Patterns of associations of clinical features in neurofibromatosis 1 (NF1)

Neurofibromatosis 1 (NF1) is a common, fully penetrant autosomal dominant disease. The clinical course is generally progressive but highly variable, and the pathogenesis is poorly understood. We studied statistical associations among 13 of the most common or important clinical features in data from four separate sets of NF1 patients: a "developmental sample" of 1,413 probands from the NNFF International Database, an independent "validation sample" of 1,384 probands from the same database, 511 affected relatives of these probands, and 441 patients from a population-based registry in northwest England. We developed logistic regressive models for each of the 13 features using the developmental sample and attempted to validate these models in the other three samples. Age and gender were included as covariates in all models. Models were successfully developed and validated for ten of the 13 features analysed. The results are consistent with grouping nine of the clinical features into three sets: (1) café-au-lait spots, intertriginous freckling and Lisch nodules; (2) cutaneous, subcutaneous and plexiform neurofibromas; (3) macrocephaly, optic glioma and other neoplasms. In addition, three-way interactions among café-au-lait spots, intertriginous freckling and subcutaneous neurofibromas indicate that the first two groups are not independent. Our studies show that some individuals with NF1 are more likely than others to develop certain clinical features of the disease. Some NF1 features appear to share pathogenic mechanisms that are not common to all features.     

Genotype-phenotype associations in neurofibromatosis type 1 (NF1): an increased risk of tumor complications in patients with <Emphasis Type="Italic">NF1</Emphasis>splice-site mutations?

Neurofibromatosis type 1 (NF1) is a complex neurocutaneous disorder with an increased susceptibility to develop both benign and malignant tumors but with a wide spectrum of inter and intrafamilial clinical variability. The establishment of genotype-phenotype associations in NF1 is potentially useful for targeted therapeutic intervention but has generally been unsuccessful, apart from small subsets of molecularly defined patients. The objective of this study was to evaluate the clinical phenotype associated with the specific types of NF1 mutation in a retrospectively recorded clinical dataset comprising 149 NF1 mutation-known individuals from unrelated families. Each patient was assessed for ten NF1-related clinical features, including the number of café-au-lait spots, cutaneous and subcutaneous neurofibromas and the presence/absence of intertriginous skin freckling, Lisch nodules, plexiform and spinal neurofibromas, optic gliomas, other neoplasms (in particular CNS gliomas, malignant peripheral nerve sheath tumors (MPNSTs), juvenile myelomonocytic leukemia, rhabdomyosarcoma, phaechromocytoma, gastrointestinal stromal tumors, juvenile xanthogranuloma, and lipoma) and evidence of learning difficulties. Gender and age at examination were also recorded. Patients were subcategorized according to their associated NF1 germ line mutations: frame shift deletions (52), splice-site mutations (23), nonsense mutations (36), missense mutations (32) and other types of mutation (6). A significant association was apparent between possession of a splice-site mutation and the presence of brain gliomas and MPNSTs (p?=?0.006). If confirmed, these findings are likely to be clinically important since up to a third of NF1 patients harbor splice-site mutations. A significant influence of gender was also observed on the number of subcutaneous neurofibromas (females, p?=?0.009) and preschool learning difficulties (females, p?=?0.022).     

Scanning the first part of the neurofibromatosis type 1 gene by RNA-SSCP: Identification of three novel mutations and of two new polymorphisms

Neurofibromatosis type 1 (NF1) of von Recklinghausen is a common autosomal dominant disorder, characterized by peripheral neurofibromas, café-au-lait spots and Lisch nodules of the iris. The high mutation rate at the NF1 locus results in a wide range of molecular abnormalities. We have scanned 14 different exons from the first part of the NF1 gene using the RNA-single strand conformation polymorphism (RNA-SSCP) method in a series of 40 NF1 patients. Three novel mutations, two nonsense and one missense, and two polymorphisms have been detected in familial cases. Genotype-phenotype correlations have been investigated, but no particular association has been detected. After this screening, the majority of NF1 chromosomes has not yet been characterized, confirming the difficulty in detecting the defect underlying NF1 in most families, even following extensive DNA analysis. Received: 4 August 1995 / Revised: 19 September 1995     

一个I型神经纤维瘤病家系的基因突变分析

目的：I型神经纤维瘤病是一种常见的常染色体显性遗传病,主要累及皮肤和神经系统。其临床表现多样,主要以”咖啡牛奶斑”、皮肤神经纤维瘤、虹膜Lisch结节、腋窝和腹股沟斑点为特征,I型神经纤维瘤病由NF1基因突变所致,神经纤维瘤蛋白是NFI基因编码蛋白,是一种肿瘤抑制蛋白,可抑制细胞的过度生长。NF1基因突变不仅可导致细胞过度生长,还可增加良性及恶性肿瘤的发生风险。本研究中,我们通过基因突变分析,确定中国东北地区一个伴有先天性白内障的I型神经纤维瘤家系NF1基因的突变位点。方法：通过聚合酶链反应（PCR）和NF1基因直接测序分析对家系中的3名患者及2名健康成员进行基因突变检测,以确定其突变位点。结果：此家系呈常染色体显性遗传。通过基因序列分析发现NF1基因第1140密码子第二个碱基呈杂合子点突变C—G,导致一个无义突变S1140X,家系中健康成员和正常对照未检测到此突变存在。结论：通过NF1基因测序分析,我们发现NF1基因的S1140X突变是引起该家系NF1疾病的致病原因,该突变导致NF1基因终止密码提前,神经纤维瘤素蛋白截短。本研究丰富了我国关于I型神经纤维瘤病在眼科的临床表现。     

Diagnostic Accuracy of CT-Guided Transthoracic Needle Biopsy for Solitary Pulmonary Nodules

To evaluate the diagnostic accuracy of computed tomography (CT)-guided percutaneous lung biopsy for solitary pulmonary nodules. Three hundred and eleven patients (211 males and 100 females), with a mean age of 59.6 years (range, 19–87 years), who were diagnosed with solitary pulmonary nodules and underwent CT-guided percutaneous transthoracic needle biopsy between January 2008 and January 2014 were reviewed. All patients were confirmed by surgery or the clinical course. The overall diagnostic accuracy and incidence of complications were calculated, and the factors influencing these were statistically evaluated and compared. Specimens were successfully obtained from all 311 patients. A total of 217 and 94 cases were found to be malignant and benign lesions, respectively, by biopsy. Two hundred and twenty-five (72.3%) carcinomas, 78 (25.1%) benign lesions, and 8 (2.6%) inconclusive lesions were confirmed by surgery and the clinical course. The diagnostic accuracy, sensitivity, and specificity of CT-guided percutaneous transthoracic needle biopsy were 92.9%, 95.3%, and 95.7%, respectively. The incidences of pneumothorax and self-limiting bleeding were 17.7% and 11.6%, respectively. Taking account of all evidence, CT-guided percutaneous lung biopsy for solitary pulmonary nodules is an efficient, and safe diagnostic method associated with few complications.     

Clinical characteristics predicting internal neurofibromas in 357 children with neurofibromatosis-1: results from a cross-selectional study

ABSTRACT: OBJECTIVE: To identify clinical characteristics associated with internal neurofibromas in children with NF1, as a means of ensuring the early identification of patients at high risk for malignant peripheral nerve-sheath tumors developed from preexisting internal neurofibromas.Patients and methodsWe used data from two NF1 populations, in France and North America, respectively. The French database comprised 1083 patients meeting NIH diagnostic criteria for NF1 and the Neurofibromatosis Institute Database of North America comprised 703 patients. Patients younger than 17 years of age were eligible for our study if they had been evaluated for internal neurofibromas using computed tomography and/or magnetic resonance imaging. Clinical characteristics associated with internal neurofibromas by univariate analysis (P [LESS-THAN OR EQUAL TO] 0.15) were entered into a multiple logistic regression model after checking for potential interactions and confounding. Multiple imputation was used for missing values. RESULTS: Among the 746 children in the two databases, 357 (48%) met our inclusion criteria. Their mean age was 7.7 [PLUS-MINUS SIGN] 5.0 years and there were 192 (53.8%) males. Internal neurofibromas were present in 35 (9.8%) patients. Internal neurofibromas developed earlier in females than in males and their prevalence increased during adolescence. Factors independently associated with internal neurofibromas were age (OR = 1.16 [1.07-1.27]), xanthogranulomas (OR = 5.85 [2.18-15.89]) and presence of both subcutaneous and plexiform neurofibromas (OR = 6.80 [1.52-30.44]). CONCLUSIONS: Several easily recognizable clinical characteristics indicate a high risk of internal neurofibromas in children with NF1 and, therefore, a need for very close monitoring.     

Value of injection hepato-lymphography during percutaneous transhepatic cholangiography in patients with cholestasis

Injection hepatography (IH) was made in 278 patients with cholestasis to study the drainage function of the liver. In 208 cases. IH was performed as a test during percutaneous transhepatic cholangiography (PTHC). The hepatic lymph pathways were imaged in 167 (60%) patients. Images of the biliary tract were obtained in 245 (88.1%) patients with cholestasis, it being not dilated in 34 (12.2%) patients. The fact that hepatolymphography may be performed during PTHC as an independent test permits verification of hepatic lymph circulatory disorders that are an index of the rate of inflammation in the organ.     

Solitary thyroid nodules in 93 children and adolescents. a 35-years experience

Over a period of 35 years from 1963 to 1998, 93 patients under the age of 18 years, 74 girls and 19 boys, were seen for evaluation of a solitary nodule of the thyroid gland. All patients had preoperative scintiscans of the thyroid gland and had their solitary nodule excised. Seventy-seven of the patients had a cold nodule on scintiscanning. The most common cause of solitary thyroid nodules was follicuar adenoma (68.9%). Fifteen of the 77 cold nodules were malignant (19.9%). The frequency of carcinoma in males was 26.3%, while in females it was 13.5%. Our experience suggests that the incidence of thyroid carcinoma may be decreasing in pediatric patients not exposed to known risk factors. Available diagnostic methods for attempting differentiation of benign from malignant solitary nodules are reviewed and recommendations to the clinical management are presented.     

住院糖尿病患者中甲状腺结节的流行病学研究

目的:观察住院糖尿病患者中甲状腺结节的患病率,探讨二者间潜在的关系。方法:于2008年8月~2011年12月间对上海交通大学附属第一人民医院南院因糖尿病收治入院的全部患者进行甲状腺相关病史收集、血清甲状腺激素检测及超声波检查,以筛查甲状腺结节。结果:在收治的660例糖尿病患者中,住院期间发现并诊断合并有甲状腺结节患者为221例,患病率为33.5%。进一步分析糖尿病患者临床特征与甲状腺结节关系,男性为29.8%,女性为38.4%,明显高于男性患者,二者相比差异有统计学意义(P<0.05);糖尿病患者甲状腺结节患病率有随年龄增长而升高的趋势,与≤30岁年龄组相比,年龄51岁~70岁组及≥70岁组结节患病率均明显升高,差异有统计学意义(41.1%,37.6%15.4%,均P<0.05);1型糖尿病患者甲状腺结节患病率为24.1%,2型糖尿病中为35.3%,高于1型糖尿病,差异有统计学意义(P<0.05);糖尿病患者中,不同体重指数、病程、治疗方法组中甲状腺结节患病率相互比较均无明显差异性(均P>0.05)。结论:住院糖尿病患者中甲状腺结节患病率较高,尤其是女性、较大年龄及2型糖尿病患者更为突出,临床上有必要对这些患者进行甲状腺结节的筛查。     

Intermittent hypoxia upregulates hepatic heme oxygenase-1 and ferritin-1, thereby limiting hepatic pathogenesis in rats fed a high-fat diet

Non-alcoholic fatty liver disease (NAFLD) is prevalent in patients with sleep apnea syndrome (SAS). Intermittent hypoxia (IH) and a high-fat diet (HFD) reproduce SAS and NAFLD, respectively, in rodents. In this study, rats were fed either an HFD or a standard diet (SD) for 2 weeks, and breathed either IH air or normoxic air for 4 days (early phase) or 6 weeks (late phase), with the same diets maintained during the exposure. HFD increased hepatic lipid accumulation, as detected by oil-red staining and triglyceride content. However, IH exposure reversed the hepatic steatosis at the late phase in these HFD-rats. IH exposure also increased hepatic expression of HO-1 and iron-binding protein ferritin-1 at the late phase, in association with increase in serum iron, bilirubin, and hepatic levels of lipid peroxides, such as 4-hydroxy-2-nonenal (HNE). IH exposure increased serum levels of hemoglobin (Hb) at the early phase and immunofluorescence of Hb and HO-1 in CD68-positive Kupffer cells (KCs) at the late phase. These findings support that IH induces erythrocytosis, erythro-phagocytosis, and generation of Hb in the KCs. The Hb promotes HO-1 expression in KCs, thereby produces iron, bilirubin, and carbon monoxide (CO). The iron would be either sequestrated by ferritin-1, transferred to the bone marrow for erythropoiesis, or would produce hydroxyradicals and HNE in the liver of rats fed an HFD. HNE might also contribute to the upregulation of HO-1, transferrin-1, and IκB, thereby limiting hepatic steatosis and inflammation via inhibition of nuclear factor κB (NFκB) activation.     

Agri-environmental grass hay: nutritive value and intake in comparison with hay from intensively managed grassland

Chemical composition, digestibility, nutritive value and intake of hay from an agri-environmental management (EH) were compared with those from hay (Lolium perenne) from an intensive management (IH). IH was of low to moderate quality because of unfavourable weather conditions. EH was harvested mid-June of 2000 (EH1) and 2001 (EH2) on the same sward that had not received mineral fertilizer for 10 years. The EH was characterized by a species-rich botanical composition. On average, it had lower contents of protein (32%), NDF (9%) and ash (35%), and a higher concentration of water-soluble carbohydrates (117%) than IH. Digestibility of dry and organic matter, determined with sheep, was not different between IH and EH and averaged 59 and 63%, respectively. Crude fibre and NDF digestibility were lower in EH (58 and 57%, respectively) than in IH (70 and 69%, respectively). Net energy value for lactation did not differ between IH and EH and amounted to 4.78 MJ per kg DM. True protein digested in the small intestine and rumen degraded protein balance were lower in EH (63 and -60 g per kg DM) than in IH (71 and -33 g per kg DM). Intake of hay was investigated in Holstein-Friesian heifers and Belgian Blue double-muscled heifers (mean BW 280 +/- 22 kg and 269 +/- 21 kg, respectively), and in Belgian Blue non-lactating and non-pregnant double-muscled cows (initial BW 642 +/- 82 kg), using a cross-over design. Hay was freely available. It was supplemented with 1 kg concentrate daily. Dry matter intake from hay was higher for EH than for IH in heifers (4% and 13%, respectively in Holstein-Friesian and Belgian Blue heifers) and in cows (22%). Hay from an agri-environmental management may be used for low-performing animals, as energy intake only exceeded maintenance requirements by 20 to 35%. Several characteristics of EH were different between years, such as dry matter digestibility, net energy value for lactation and fermentable organic matter content.     

超声引导下18针与20针穿刺活检对甲状腺结节的诊断效果比较

摘要 目的：比较超声引导下18针与20针穿刺活检对甲状腺结节的诊断效果。方法：选取我院超声科2018.8.6-2020.9.30共收治的167例甲状腺结节患者作为研究对象,将患者分为18针穿刺组（n=86）和20针穿刺组（n=81）,分别对两组患者应用超声引导下18针和20针穿刺活检,比较不确定结果的发生率,包括非诊断性或异型性/滤泡性病变的未确定显著性,恶性肿瘤的诊断性能在最终诊断的结节中进行评估。比较两组并发症发生率及超声引导下的核心针穿刺活检标本产率。结果：对比20针穿刺组和18针穿刺组患者的临床特征发现,两组患者性别、年龄、结节大小、结节形状、方位、回声强度、表现和钙化情况对比无明显差异（P＜0.05）;在20针穿刺组中43个结节和18针穿刺组中46个结节最终确诊。恶性结节的比例在两组之间没有显著差异。在最终诊断分析中,20针穿刺组有38个结节,18针穿刺组中有40个结节。在20针穿刺组,38个结节包括6个非诊断结果、18个不典型/滤泡性病变（未确定显著性）和14个滤泡性肿瘤。在18针穿刺组中,40个结节包括1个非诊断结果,22个不典型/滤泡性病变未确定的显著性,17个滤泡性肿瘤;18针穿刺组的未确诊率（包括非诊断结果和未发现显著性的异型性/滤泡性病变）较低（29.1 % vs 37.0 %）,尽管这一差异在统计学上没有显著性（P＞0.05）。然而,18针穿刺组的非诊断性结果发生率（1.2 % vs 8.6 %;P＜0.05）显著低于20针穿刺组。两组的不典型/滤泡性病变的发生率（27.8 % vs 28.4 %）相似。20针穿刺组的CNB显示出更高的敏感性（75.0 % vs 66.7 %）,更高的阴性预测值（NPV;83.9 % vs 75.9 %）和更高的准确率（78.3 % vs 74.4 %）,虽然结果没有达到统计显著性。两组的特异性（81.8 % vs 80.8 %）和阳性预测值（PPV;两者均为100 %）相似;18针穿刺组和20针穿刺组患者的并发症发生率对比无明显差异（P＞0.05）。结论：18针芯针活检对甲状腺结节的诊断较20针更有效,且不增加并发症情况,安全性好,值得临床应用推广。     

Agri-environmental grass hay: nutritive value and intake in comparison with hay from intensively managed grassland

Chemical composition, digestibility, nutritive value and intake of hay from an agri-environmental management (EH) were compared with those from hay (Lolium perenne) from an intensive management (IH). IH was of low to moderate quality because of unfavourable weather conditions. EH was harvested mid-June of 2000 (EH1) and 2001 (EH2) on the same sward that had not received mineral fertilizer for 10 years. The EH was characterized by a species-rich botanical composition. On average, it had lower contents of protein (32%), NDF (9%) and ash (35%), and a higher concentration of water-soluble carbohydrates (117%) than IH. Digestibility of dry and organic matter, determined with sheep, was not different between IH and EH and averaged 59 and 63%, respectively. Crude fibre and NDF digestibility were lower in EH (58 and 57%, respectively) than in IH (70 and 69%, respectively). Net energy value for lactation did not differ between IH and EH and amounted to 4.78 MJ per kg DM. True protein digested in the small intestine and rumen degraded protein balance were lower in EH (63 and ??60?g per kg DM) than in IH (71 and ??33?g per kg DM). Intake of hay was investigated in Holstein-Friesian heifers and Belgian Blue double-muscled heifers (mean BW 280?±?22?kg and 269?±?21?kg, respectively), and in Belgian Blue non-lactating and non-pregnant double-muscled cows (initial BW 642?±?82?kg), using a cross-over design. Hay was freely available. It was supplemented with 1?kg concentrate daily. Dry matter intake from hay was higher for EH than for IH in heifers (4% and 13%, respectively in Holstein-Friesian and Belgian Blue heifers) and in cows (22%). Hay from an agri-environmental management may be used for low-performing animals, as energy intake only exceeded maintenance requirements by 20 to 35%. Several characteristics of EH were different between years, such as dry matter digestibility, net energy value for lactation and fermentable organic matter content.     

A Retrospective Study of Clinicopathologic Outcomes of Nodules With Hürthle Cell Cytology and the Thyroid Nodule App (TNAPP) Ultrasound Recommendations

ObjectivesHürthle cells are a common finding on thyroid fine-needle aspiration, but when they are the predominant cytology, they represent a difficult diagnostic challenge. The Thyroid Nodule App (TNAPP) is a new, publicly available web application utilizing ultrasound (US) features based on the updated 2016 American Association of Clinical Endocrinologists clinical practice guidelines for thyroid nodule management. This pilot study was performed to assess the TNAPP recommendations and surgical pathology outcomes of Hürthle cell-predominant thyroid nodules.MethodsA retrospective review of nodules with Bethesda III (atypia of undetermined significance with Hürthle cells) or Bethesda IV (suspicious for Hürthle cell neoplasm) cytology, for which surgery was performed between 2017 and 2021, was conducted. TNAPP US categories 1, 2, and 3 (low, intermediate, and high risk, respectively) were assigned based on nodule characteristics, and clinical management recommendations were recorded. Results were compared with histology-proven diagnoses.ResultsFifty-nine nodules in 57 patients where surgical pathology was available were analyzed with the TNAPP algorithm. Of the 59 nodules, 4 were US category 1 (low risk/suspicion), 40 were US category 2 (intermediate risk/suspicion), and 15 were US category 3 (high risk/suspicion). All US category 1 nodules were benign, while 30% of the US category 2 and 40% of the US category 3 nodules were malignant. Of the patients who had molecular marker testing with ThyroSeq, 22 out of 29 (76%) were positive, indicating either an intermediate or high risk of malignancy, 7 of which were malignant.ConclusionThis preliminary study suggests that TNAPP is a useful clinical tool for sonographic assessment of thyroid nodules with Hürthle cell cytology.