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PubMed1982

Kinetics of phenotypic maturation of remodeling of hyperplastic nodules during liver carcinogenesis.

Hyperplastic nodules appearing during the preneoplastic phase of liver carcinogenesis were divided into two types, persistent and remodeling, according to the pattern of staining for gamma-glutamyltransferase. In the resistant cell model of liver carcinogenesis used in this study, hyperplastic nodules, uniformly staining for gamma-glutamyltransferase, rapidly emerge by 4 weeks after a single injection of diethylnitrosamine and brief selection by dietary 2-acetylaminofluorene plus partial hepatectomy. By 6 weeks, a majority of nodules (about 75%) show an obvious irregularity and loss of uniformity in staining for gamma-glutamyltransferase while the remaining nodules continue to be uniformly stained. The number of irregularly stained nodules increases over the next 18 weeks until over 95% of nodules show the nonuniform loss of enzyme activity. The progressive loss of enzyme activity is accompanied by architectural remodeling to normal-appearing liver. This is associated with the increasing disappearance of many obvious nodules from the liver as the remodeling ones blend imperceptibly with the surrounding liver. The uniformly stained nodules show the persistence of hepatocyte arrangements in plates two or more cells thick and in acini and of cytoplasmic hypertrophy characteristic of persistent hyperplastic nodules. Labeling indices are much higher in hepatocytes of the persistent uniformly stained nodules than in the remodeling ones. The possibility of exploiting this phase of the model further for in-depth analysis of the nodule-to-carcinoma sequence is discussed.

2-Acetylaminofluorene↗

PubMed1980

Observations on Onchocerca gibsoni and nodule development in naturally-infected cattle in Australia.

O. gibsoni worms were extracted from 185 nodules of a total of 370 worm nodules collected from 94 naturally infected cattle at Townsville, Australia. 183 of the 185 nodules contained a single female worm, 60% of them contained a single male worm and 7% contained two male worms. Nodules containing males alone were not found. Small nodules (less than 0.2 g) contained immature female worms without microfilariae and no males. As nodule size and female worm size increased, the number of female worms with microfilariae and the number of nodules with males increased reaching almost 100% in nodules weighing greater than 3.0 g. It is suggested that female worms normally become encapsulated when young, grow within the nodule and tht the male enters the nodule later, fertilises the female and remains in the nodule.

Animals↗

PubMedDate not supplied

American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules.

Thyroid nodules are common and are frequently benign. Current data suggest that the prevalence of palpable thyroid nodules is 3% to 7% in North America; the prevalence is as high as 50% based on ultrasonography (US) or autopsy data. The introduction of sensitive thyrotropin (thyroid-stimulating hormone or TSH) assays, the widespread application of fine-needle aspiration (FNA) biopsy, and the availability of high-resolution US have substantially improved the management of thyroid nodules. This document was prepared as a collaborative effort between the American Association of Clinical Endocrinologists (AACE) and the Associazione Medici Endocrinologi (AME). Most Task Force members are members of AACE. We have used the AACE protocol for clinical practice guidelines, with rating of available evidence, linking the guidelines to the strength of recommendations. Key observations include the following. Although most patients with thyroid nodules are asymptomatic, occasionally patients complain of dysphagia, dysphonia, pressure, pain, or symptoms of hyperthyroidism or hypothyroidism. Absence of symptoms does not rule out a malignant lesion; thus, it is important to review risk factors for malignant disease. Thyroid US should not be performed as a screening test. All patients with a palpable thyroid nodule, however, should undergo US examination. US-guided FNA (US-FNA) is recommended for nodules > or = 10 mm; US-FNA is suggested for nodules < 10 mm only if clinical information or US features are suspicious. Thyroid FNA is reliable and safe, and smears should be interpreted by an experienced pathologist. Patients with benign thyroid nodules should undergo follow-up, and malignant or suspicious nodules should be treated surgically. A radioisotope scan of the thyroid is useful if the TSH level is low or suppressed. Measurement of serum TSH is the best initial laboratory test of thyroid function and should be followed by measurement of free thyroxine if the TSH value is low and of thyroid peroxidase antibody if the TSH value is high. Percutaneous ethanol injection is useful in the treatment of cystic thyroid lesions; large,symptomatic goiters may be treated surgically or with radioiodine. Routine measurement of serum calcitonin is not recommended. Suggestions for thyroid nodule management during pregnancy are presented. We believe that these guidelines will be useful to clinical endocrinologists, endocrine surgeons, pediatricians, and internists whose practices include management of patients with thyroid disorders. These guidelines are thorough and practical, and they offer reasoned and balanced recommendations based on the best available evidence.

Biopsy, Fine-Needle↗

PubMedDate not supplied

Thyroid nodules in Graves disease and the risk of thyroid carcinoma.

BACKGROUND: The risk of thyroid carcinoma in patients with Graves disease has been particularly emphasized when nodules coexist with thyroid hyperplasia; a surgical approach has been suggested. OBJECTIVES: To detect thyroid nodules early in patients with Graves disease and to evaluate the risk of carcinoma. METHODS: The study group included 315 consecutive outpatients with Graves hyperthyroidism not previously treated with surgery or radioiodine therapy. Thyroid ultrasonography was performed at the time of enrollment and repeated annually in all patients; fine-needle aspiration (FNA) was carried out in those patients with nodules and repeated after 2 years or at shorter intervals. RESULTS: One hundred six of 315 patients with Graves disease had thyroid nodules 8 mm in diameter or larger detected by ultrasonography. In 49 patients, nodules were present at the time of the first examination; in 57 patients, nodules developed during follow-up. Fine-needle aspiration cytology results revealed features of carcinoma in only 1 patient; this was confirmed by histologic examination of excised thyroid tissue. The nodules with normal cytologic features at the time of the first examination did not show any clinical and/or cytologic evolution toward malignancy during follow-up. CONCLUSIONS: Ultrasonographic evidence of nodules was frequently found among our patients with Graves disease, but malignant FNA cytologic findings of the examined nodules were rare at the time of diagnosis and throughout the course of the disease. When FNA cytologic evaluation does not indicate malignancy, the presence of thyroid nodules in patients with Graves disease does not indicate an aggressive therapeutic approach.

Adult↗

PubMed2006

Radiation dose-response relationships for thyroid nodules and autoimmune thyroid diseases in Hiroshima and Nagasaki atomic bomb survivors 55-58 years after radiation exposure.

CONTEXT: Effects of irradiation on thyroid diseases such as thyroid nodules and autoimmune thyroid diseases have not been evaluated among people exposed to radiation more than 50 years in the past. OBJECTIVE: To evaluate the prevalence of thyroid diseases and their radiation-dose responses in atomic bomb survivors. DESIGN, SETTING, AND PARTICIPANTS: Survey study comprising 4091 cohort members (mean age, 70 [SD, 9] years; 1352 men and 2739 women) who participated in the thyroid study at the Radiation Effects Research Foundation. Thyroid examinations were conducted between March 2000 and February 2003. MAIN OUTCOME MEASURES: Prevalence of thyroid diseases, including thyroid nodules (malignant and benign) and autoimmune thyroid diseases, and the dose-response relationship of atomic bomb radiation in each thyroid disease. RESULTS: Thyroid diseases were identified in 1833 (44.8%) of the total participants (436 men [32.2% of men] and 1397 women [51.0% of women]) (P<.001). In 3185 participants, excluding persons exposed in utero, not in the city at the time of the atomic bombings, or with unknown radiation dose, the prevalence of all solid nodules, malignant tumors, benign nodules, and cysts was 14.6%, 2.2%, 4.9%, and 7.7%, respectively. The prevalence of positive thyroid antibodies, antithyroid antibody-positive hypothyroidism, and Graves disease was 28.2%, 3.2%, and 1.2%, respectively. A significant linear dose-response relationship was observed for the prevalence of all solid nodules, malignant tumors, benign nodules, and cysts (P<.001). We estimate that about 28% of all solid nodules, 37% of malignant tumors, 31% of benign nodules, and 25% of cysts are associated with radiation exposure at a mean and median thyroid radiation dose of 0.449 Sv and 0.087 Sv, respectively. No significant dose-response relationship was observed for positive antithyroid antibodies (P = .20), antithyroid antibody-positive hypothyroidism (P = .92), or Graves disease (P = .10). CONCLUSIONS: A significant linear radiation dose response for thyroid nodules, including malignant tumors and benign nodules, exists in atomic bomb survivors. However, there is no significant dose response for autoimmune thyroid diseases.

Aged↗

PubMed1998

Assessment of fine-needle aspiration sampling technique in thyroid nodules.

BACKGROUND: A prospective two-yr study was undertaken to assess the heterogeneity of thyroid nodules using the fine-needle aspiration (FNA) technique of systematic regional sampling. In addition, we determined the number of regions to be sampled to minimize non-diagnostic results, and to optimally characterize thyroid nodules. DESIGN: FNA was performed on 74 nodules > or = 1.5 cm. in diameter in five distinct regions in sequence (center, then four quadrants starting at 12:00, clockwise). Slides from each region were coded, randomized, subjected to blind review, and categorized as non-diagnostic (ND), benign (B), indeterminate (ID), suspicious/neoplastic (S/N), or malignant (M). Final cytologic diagnosis (CD) was made from all slides of each nodule. RESULTS: The ND rate for center FNAs alone was 16%, but addition of the 12:00 region decreased it to 5.3%. With 3, 4, or 5 sequential sites the nondiagnostic rates were 4, 2.6, and 2.6%. The center region diagnosis was identical to the final CD in 71% of the cases. Addition of the 12:00 region increased the concordance to 88%. Three sequential regions equaled the CD in 93% of cases, and 4 regions equaled the CD in 99% of cases. All nodules characterized as M or S/N were resected as were 76% of the ID nodules. Of the 43 nodules characterized as B, 3 were resected, 24 involuted, 6 were unchanged, and 10 were lost to follow-up. All 3 M nodules proved malignant by histology, as did 7/10 S/N, 0/17 ID, and 0/43 B nodules; 3/10 S/N, 1/17 ID and 1/43 B were adenomas. Likelihood ratios for diagnosing neoplasia were ND:0, B:0.10, ID:0.21, S/N:infinity, M:infinity. CONCLUSIONS: Sampling of at least four distinct regions accurately assesses thyroid nodules while minimizing ND results. Regional sampling also addresses intranodular heterogeneity.

Biopsy, Needle↗

PubMed1994

Limitations of thyroid scanning in solitary thyroid nodules.

During an 8-year period, 104 patients (19 males, 85 females) underwent surgery for a solitary thyroid nodule. There were 19 (18.3%) malignant nodules and 85 (81.7%) benign nodules. Malignancy occurred in 3 (15.8%) males and 16 (18.8%) females. Pre-operative scanning was performed prior to referral in 59 patients (52 had ultrasound, 41 had isotope scanning; the majority had both). Of the scanned patients, 12 (20%) had a malignant nodule while 7 (15.5%) of the 45 patients who did not have scanning had a malignant nodule. In patients who had an ultrasound scan, malignancy was found in 5 (23.8%) of the 21 solid nodules and 7 (22.7%) of the 31 cystic (or solid/cystic) nodules. In patients who had thyroid isotope scanning, malignancy was found in 6 (17.5%) of the 34 cold (non-functioning) nodules and 3 (43%) of the 7 warm or hot (functioning) nodules. Ultrasound and isotope scanning may be misleading and neither help to differentiate benign from malignant thyroid nodules which require surgical excision.

Adolescent↗

PubMed2003

A comparison of radionuclide thyroid angiography, (99m)Tc-MIBI scintigraphy and power Doppler ultrasonography in the differential diagnosis of solitary cold thyroid nodules.

We prospectively studied 43 patients with solitary cold thyroid nodules greater than 1.5 cm in diameter to determine the comparative diagnostic value of radionuclide thyroid angiography (RTA), technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) scintigraphy and power Doppler ultrasonography (PDUS) in the differentiation of benign and malignant thyroid nodules. Perfusion of the nodules in RTA was compared with the perfusion in the surrounding normal thyroid tissue and classified as follows: 0, avascular; 1, hypovascular; 2, isovascular; 3, hypervascular. (99m)Tc-MIBI uptake in the nodules compared with that in surrounding thyroid tissue was scored for both early and delayed images as follows: 0, cold; 1, decreased; 2, equal; 3, increased. PDUS patterns were classified as nodule vascularisation patterns. The malignancy criteria were set as follows: hypervascular nodule with rapid washout in RTA; complex ring sign with anarchic structure or delta sign in PDUS, and positive retention and increased uptake in the nodule in the early and delayed (99m)Tc-MIBI images. These data were compared with the histopathological results. Histology revealed thyroid carcinoma in nine patients (five cases of papillary carcinoma, three of follicular carcinoma and one of medullary carcinoma) and benign conditions in 34 patients (30 cases of nodular goitre, three of lymphocytic thyroiditis and one of follicular adenoma). Sensitivity, specificity and accuracy were, respectively, 0.89, 1.00 and 0.97 for RTA, 1.00, 0.76 and 0.81 for PDUS, and 0.67, 0.91 and 0.86 for (99m)Tc-MIBI scintigraphy (when nodules with increased uptake in both the early and the delayed images and a positive retention index were considered as malignant). RTA, (99m)Tc-MIBI scintigraphy and PDUS could be helpful in the preoperative assessment of solitary cold thyroid nodules. In this study, RTA was found to be the most accurate and specific method for differentiation of malignant from benign thyroid nodules.

Adult↗

PubMed2006

Accuracy of transmission CT and FDG-PET in the detection of small pulmonary nodules with integrated PET/CT.

PURPOSE: The purpose of this study was to determine the accuracy of detection of small pulmonary nodules on quiet breathing attenuation correction CT (CTAC) and FDG-PET when performing integrated PET/CT, as compared with a diagnostic inspiratory CT scan acquired in the same imaging session. METHODS: PET/CT scans of 107 patients with a history of carcinoma (54 male and 53 female, mean age 57.3 years) were analyzed. All patients received an integrated PET/CT scan including a CTAC acquired during quiet respiration and a contrast-enhanced CT acquired during inspiration in the same session. Breathing CTAC scans were reviewed by two thoracic radiologists for the presence of pulmonary nodules. FDG-PET scans were reviewed to determine accuracy of nodule detection. Diagnostic CT was used as the gold standard to confirm or refute the presence of nodules. RESULTS: On the CTAC scans 200 nodules were detected, of which 183 were true positive (TP) and 17, false positive. There were 109 false negatives (FN). Overall, 51 (48%) patients had a false interpretation, including 19 in whom CT was interpreted as normal for lung nodules. The average size of the nodules missed was 3.8+/-2 mm (range 2-12 mm). None of the nodules missed on the CTAC scans were detected by PET. In the right lung there were 20 TP, 42 true negative (TN), 11 FP, and 34 FN interpretations with a sensitivity in nodule detection of 37% (CI 24-51%) and a specificity of 79% (CI 66-89%). In the left lungs there were 16 TP, 65 TN, 3 FP, and 23 FN interpretations, with a sensitivity of 41% (CI 26-58%) and a specificity of 96% (CI 88-99%). CONCLUSION: The detection of small pulmonary nodules by breathing CTAC and FDG-PET is relatively poor. Therefore an additional diagnostic thoracic CT scan obtained during suspended inspiration is recommended for thorough evaluation of those patients in whom detection of pulmonary metastases is necessary for management.

Adolescent↗

PubMed2003

Detection of pulmonary nodules by multislice computed tomography: improved detection rate with reduced slice thickness.

The purpose of this study was to find out if the use of 1.25-mm collimated thin-slice technique helps to detect more small pulmonary lung nodules than the use of 5 mm. A total of 100 patient examinations that allowed a reconstruction of 1.25-mm slice thickness in addition to the standard of 5-mm slices were included in a prospective study. Acquisition technique included four rows of 1-mm slices. Two sets of contiguous images were reconstructed and compared with 1.25- and 5-mm slice thickness, respectively. Two radiologists performed a film-based analysis of the images. The size and the confidence of the seen nodules were reported. We did not perform a histological verification, according to the normal clinical procedure, although it would be optimal regarding research. Statistical analysis was performed by using longitudinal analysis described by Brunner and Langer. In addition, sensitivity, specificity, negative predictive value and positive predictive value were calculated for each reader using the 1.25-mm sections as the gold standard. As an index for concordance the kappa value was used. A value of p<0.05 was regarded as significant. In 37 patients pulmonary nodules were detected. Twenty-four patients showed more than one nodule; among these, 7 patients had disseminated disease and were excluded from the study. Pulmonary nodules larger than 10 mm in size were equally well depicted with both modalities, whereas lesions smaller than 5 mm in size were significantly better depicted with 1.25 mm (p<0.05). Using 1.25 mm as the gold standard, sensitivity for 5-mm reconstruction interval was 88 and 86% for observers A and B, respectively. No false-positive results were reported for 5-mm sections. Interobserver agreement for nodule detection determined for 1.25-mm reconstruction intervals showed a k value of 0.753, indicating a good agreement, and 0.562 for 5-mm reconstruction intervals, indicating a moderate agreement. Brunner and Langer analysis showed significant differences for slice thickness and no significant difference between the observers. Reduced slice thickness demonstrated an improvement of small nodule detection, confidence levels, and interobserver agreement. Application of thin-slice multidetector-row CT may raise the sensitivity for lung nodule detection, although the higher detection rate of smaller nodules has to be evaluated from a clinical perspective and remains problematic about how the detection of small nodules will effect patient outcome.

Adult↗

PubMed2003

Volumetric measurements of pulmonary nodules at multi-row detector CT: in vivo reproducibility.

The aim of this study was to assess the in vivo measurement precision of a software tool for volumetric analysis of pulmonary nodules from two consecutive low-dose multi-row detector CT scans. A total of 151 pulmonary nodules (diameter 2.2-20.5 mm, mean diameter 7.4+/-4.5 mm) in ten subjects with pulmonary metastases were examined with low-dose four-detector-row CT (120 kVp, 20 mAs (effective), collimation 4x1 mm, normalized pitch 1.75, slice thickness 1.25 mm, reconstruction increment 0.8 mm; Somatom VolumeZoom, Siemens). Two consecutive low-dose scans covering the whole lung were performed within 10 min. Nodule volume was determined for all pulmonary nodules visually detected in both scans using the volumetry tool included in the Siemens LungCare software. The 95% limits of agreement between nodule volume measurements on different scans were calculated using the Bland and Altman method for assessing measurement agreement. Intra- and interobserver agreement of volume measurement were determined using repetitive measurements of 50 randomly selected nodules at the same scan by the same and different observers. Taking into account all 151 nodules, 95% limits of agreement were -20.4 to 21.9% (standard error 1.5%); they were -19.3 to 20.4% (standard error 1.7%) for 105 nodules <10 mm. Limits of agreement were -3.9 to 5.7% for intraobserver and -5.5 to 6.6% for interobserver agreement. Precision of in vivo volumetric analysis of nodules with an automatic volumetry software tool was sufficiently high to allow for detection of clinically relevant growth in small pulmonary nodules.

Adult↗

PubMed1992

Cancer risk in patients with cold thyroid nodules: relevance of iodine intake, sex, age, and multinodularity.

PURPOSE: We evaluated the frequency of thyroid cancer in patients with cold thyroid nodules in relation to iodine intake, sex, age, and multinodularity in a consecutive series of patients with nodular thyroid diseases. PATIENTS: In the period from 1980 to 1990, 5,637 patients were studied: 4,176 patients were from an iodine-sufficient area (ISA) and 1,461 from an adjacent iodine-deficient area (IDA). Surgery was performed in 792 patients on the basis of a suspicious or malignant finding at fine-needle aspiration biopsy. RESULTS: The overall thyroid cancer frequency was 4.6% (259 patients had cancer). Iodine intake affected the cancer rate in patients with cold nodules. The frequency of cancer in patients with cold thyroid nodules was 5.3% in the ISA and 2.7% in the IDA. This difference, however, was significant only in females. Sex had a major influence on the malignant rate of cold nodules; although female patients were more frequently observed (n = 5,028) than male patients (n = 609), the frequency of cancer was significantly lower in female patients with cold nodules (4.2%) than in males (8.2%). Age was an important factor in both sexes. The proportion of nodules that were malignant was smallest in patients of the 4th decade and was greatest in patients younger than 30 years or older than 60 years. Multivariate analysis showed that sex and age interact in determining the cancer risk in patients with thyroid nodules. Finally, the frequency of thyroid cancer in patients with a solitary nodule was not different from the frequency in patients with multiple nodules. CONCLUSION: Our study indicates that thyroid cancer risk in a patient with a nodular goiter varies markedly according to iodine intake, sex, and age but not in relation to multinodularity, as assessed by clinical examination. The knowledge of these epidemiologic aspects of thyroid cancer may increase the accuracy of the preoperative selection of patients with cold nodules of the thyroid.

Adult↗

PubMed1994

Hybrid lung nodule detection (HLND) system.

A Hybrid Lung Nodule Detection (HLND) system is developed for improving detection accuracy and speed for lung cancerous pulmonary radiology. The configuration of the HLND system includes (i) pre-processing, in order to enhance the figure-background contrast based upon the energy content of nodule; (ii) quick selection of nodule suspects based upon the most prominent feature of nodules, the disc shape; and (iii) complete feature space determination and neural network classification of nodules, based on the characteristics of edges in nodules. Nodule suspects are captured and stored in 32 x 32 images after first two processing phases. Eight categories, including true nodule, rib-crossing, rib-vessel crossing, end vessel, vessel cluster, bone, rib edge, and vessel, are identified for further neural analysis and classification. A supervised back propagation artificial neural network architecture is developed for training and recognition of feature curves of nodules. Results show that this detection system is able to identify true nodule at accuracy up to 93% with false detection reduced down to 7%.

Algorithms↗

PubMed2006

Structure, expression, and mapping of two nodule-specific genes identified by mining public soybean EST databases.

Numerous nodule-specific genes, which are involved in the root nodule development and function, have been known and are still being discovered. Here, we reported the structure, expression, and genetic map location of two novel nodule-specific genes. First, two EST groups, one obtained from a nodule library and the other from all aboveground tissue libraries, were clustered with regard to in silico expression profiles. We compiled a pool of 103 putative nodule-specific sequence clusters. Then, two representative ESTs were selected for further experimental analyses. According to the full-length cDNA sequences, one was an EST of a novel nodule-specific polygalacturonase gene, GmPGN, and the other was an EST of a new short nodule-specific gene, GmEKN. The results of expression analyses of the GmPGN cDNAs indicated that GmPGN expression was not detectable in any of the soybean tissues except in the nodule tissue and may be regulated via alternative splicing. GmEKN expression was the most strongly detected in the nodule. The predicted GmEKN protein is both glutamic acid- and lysine-rich, and is also highly hydrophilic. Genetic mapping located GmPGN near the known quantitative trait locus conferring resistance to soybean cyst nematode on soybean molecular linkage group (MLG) B1, and GmEKN on MLG A2. These results provide useful information for the use of these genes in research on the orchestration of numerous genes in nodule development and function.

Amino Acid Sequence↗

PubMed1993

Importance of repeat fine-needle biopsy in the management of thyroid nodules.

Fine-needle aspiration (FNA) biopsy of a thyroid nodule was performed in 797 patients. Ninety-six patients had resection of the thyroid nodule performed subsequent to a one-time FNA biopsy. The surgical pathology of these 96 cases demonstrated a 5.8% false-negative rate and a 9.9% false-positive rate. As a consequence, we prospectively evaluated the routine practice of repeat FNA of cytologically benign thyroid nodules. Repeat FNA confirmed the original benign cytology in 183 (93%) of 196 patients. Seventeen of these 183 patients with benign FNA on both biopsies had resection of the nodule performed because of the development of suspicious clinical signs or in response to the patient's choice; 1 recurrent cyst was found to be carcinomatous. Of the 13 patients demonstrating a change in cytology on repeat FNA biopsy, 9 had a nodule that was classified as possibly malignant (suspicious); 6 of these patients underwent resection, and 1 patient was found to have a carcinomatous nodule. Four patients had nodules that were classified as probably malignant on repeat FNA biopsy; all of their nodules were resected, and three of them were found to be carcinomatous. This study demonstrates that, although one-time FNA biopsy of thyroid nodules is highly accurate, with a relatively low false-negative rate, repeat fine-needle biopsy improves on this diagnostic accuracy, thereby decreasing the risk of misdiagnosing a thyroid nodule that is malignant.

Adult↗

PubMed2001

Pathogenesis of thyroid nodules: histological classification?

Thyroid nodule genesis may be considered as an amplification of thyroid heterogeneity due to genetic and/or epigenetic mechanisms. We classified the thyroid nodules in five types with distinct histological features: hyperplastic, neoplastic, colloid, cystic and thyroiditic nodules. Hyperplastic: Thyrocyte proliferation is under the control of TSH but several other paracrine and autocrine factors are secreted by follicular cells, the stromal apparatus and the lymphocytes, which are implicated in initiation and perpetuation of thyroid hyperplasia. Growth occurs mainly through TSHR, cAMP and PKA. Constitutive cAMP overproduction has been shown to be due to point mutation of the TSHR or Gs protein, producing overgrowth and hyperfunction. Neoplastic: Several activated oncogenes have been identified in thyroid malignancies. Oncogenes relevant to the thyroid carcinogenesis are: mutated TSHR and gsp (constitutive activation of cAMP); TRK (receptor for NGF); RET/PTC (phosphorylation of tyrosine kinase receptor)--an isoform of this oncogene is induced by radiation: ras (it encodes Gs proteins transducing mitogenic signals); and c-MET (receptor for hepatocyte growth factor). The evolution of a differentiated thyroid cancer towards an undifferentiated cancer is due to a mutation of a family of proteins (i.e., p53), which acts as a brake, preventing the genomic instability of cancer. It is suggested that a tumor initiates by RET or ras and possibly progresses--as a result of additional mutations and by p53 mutation--to anaplastic carcinoma. Colloid: Flattening of the epithelium and dilatation of follicles containing viscous material--made up by a concentrated solution of thyroglobulin (hTg)--is the characteristic of the colloid nodule. A defect of intraluminal reabsorption of hTg has been suggested but not proven. Experimentally, a load of iodine is able to change thyroid hyperplasia to a colloid feature; however, a load of iodine is rarely found in the clinical history of patients. A new clue to the pathogenesis comes from the finding that a relevant part of the colloid (10-20%) is made up of insoluble globules, where hTg is compacted in a polymeric form. It is suggested that stocking hTg into globules is defective in colloid nodules, leading to enormous enlargement of the follicle. Cystic: It is estimated that between 15 and 40% of thyroid nodules are partly or entirely cystic. The 'true cyst' is rare; most of the so-called cystic nodules are 'pseudocysts', which follow necrosis and colliquation. Necrosis issues as an imbalance between growth and the precisely regulated process of angiogenesis. More recently, the VEGF/VPF has been found to be at the origin of recent and recurrent cysts. Immunotoxic and apoptotic mechanisms have also been suggested. Chemical analysis of cystic fluid showed a 'denatured' and 'serum-like' pattern suggesting different mechanisms in the pathogenesis of the pseudocystic thyroid nodules. Thyroiditic: Nodular lymphocytic thyroiditis (NLT) includes two different entities: 1) lymphocyte thyroiditis growing as a nodule in a hyperplastic or normal gland, and 2) lymphocyte thyroiditis associated in the same nodule with other nodular diseases of the thyroid: papillary thyroid carcinoma and lymphoma have been found to be associated to chronic lymphocytic thyroiditis.

Humans↗

PubMed2001

Prospective study on video-assisted thoracoscopic surgery in the resection of pulmonary nodules: 209 cases from the Spanish Video-Assisted Thoracic Surgery Study Group.

OBJECTIVE: The diagnosis of pulmonary nodules has become one of the main indications of video-assisted thoracoscopic surgery (VATS), especially for small nodules not accessible by bronchoscopy or by percutaneous transthoracic needle aspiration. In this study we evaluate the indications, diagnostic safety, complications, and technical difficulty of VATS in the diagnosis of pulmonary nodules in Spain. MATERIALS AND METHODS: We conducted a prospective study of 209 patients with one or more pulmonary nodules from a group of Spanish thoracic surgery divisions (The Spanish Video-assisted Thoracic Surgery Study Group). Data was collected and evaluated on variables contained on a questionnaire including demographic information, characteristics of the nodules, identification methods, surgical technique, morbidity and mortality rates, and diagnostic yield. RESULTS: The mean size of the nodules was 1.9 cm (range 0.3-5 cm). A total of 93.3% were peripheral. A diagnosis was established in 100% of the cases. In this study, 51.1% of lesions were benign and 48.8% were malignant. In 16.3% of cases, a conversion to thoracotomy was needed. The morbidity was 9.6% and the mortality 0.5%. We found a relationship between the size of a nodule and a diagnosis of malignancy (P=0.019) and between a central location and a need to convert to thoracotomy (P=0.002). Patients with nodules >2 cm had a greater risk of complications (P=0.0001). CONCLUSIONS: In the diagnosis of pulmonary nodules, VATS has a specificity of 100% and a low mortality rate. The probability of developing complications is higher when the nodule is >2 cm.

Adolescent↗

PubMed2001

Ras mutations are rare in solitary cold and toxic thyroid nodules.

OBJECTIVE: Activation of ras proto-oncogenes as a result of point mutations is detectable in a significant percentage of most types of tumour. Similar to neoplasms of other organs, mutations of all three ras genes can be found in thyroid tumours. H-, K- and N-ras mutations have been detected in up to 20% of follicular adenomas and adenomatous nodules which were not functionally characterized. This raises the question as to whether ras mutations are specific for hypofunctional nodules and TSH receptor mutations for hyperfunctioning nodules. DESIGN: To investigate ras and TSH receptor mutations with respect to functional differentiation we studied 41 scintigraphically cold nodules and 47 toxic thyroid nodules. To address the likelihood of a somatic mutation we also studied the clonal origin of these tumours. MEASUREMENTS: Genomic DNA was extracted from nodular and surrounding tissue. Mutational hot spots in exons 1 and 2 of the H- and K-ras gene were PCR amplified and sequenced using big dye terminator chemistry. Denaturing gradient gel electrophoresis (DGGE) was used to verify sequencing results for the H-ras gene and to analyse the N-ras gene because its greater sensitivity in detecting somatic mutations. Clonality of nodular thyroid tissue was evaluated using X-Chromosome inactivation based on PCR amplification of the human androgen receptor locus. RESULTS: Monoclonal origin was detectable in 14 of 23 informative samples from cold thyroid nodules. In toxic thyroid nodules the frequency of clonal tissue was 20 in 30 informative cases. Only one point mutation could be found in the N-ras gene codon 61 (Gly to Arg) in a cold adenomatous nodule which was monoclonal. In toxic thyroid nodules no ras mutation was detectable. CONCLUSION: Our study suggests that ras mutations are rare in solitary cold and toxic thyroid nodules and that the frequent monoclonal origin of these tumours implies somatic mutations in genes other than H-, K- and N-ras.

Adenocarcinoma, Follicular↗