Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Gr...

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2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's guidelines for the management of these disorders was published in 2006, a large amount of new information has become available, prompting a revision of the guidelines. Methods: Relevant articles through December 2008 were reviewed by the task force and categorized by topic and level of evidence according to a modified schema used by the United States Preventative Services Task Force. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to optimal surgical management, radioiodine remnant ablation, a...

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Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer

If carcinogenesis occurs by somatic evolution, then common components of the cancer phenotype result from active selection and must, therefore, confer a significant growth advantage. A near-universal property of primary and metastatic cancers is upregulation of glycolysis, resulting in increased glucose consumption, which can be observed with clinical tumour imaging. We propose that persistent metabolism of glucose to lactate even in aerobic conditions is an adaptation to intermittent hypoxia in pre-malignant lesions. However, upregulation of glycolysis leads to microenvironmental acidosis requiring evolution to phenotypes resistant to acid-induced cell toxicity. Subsequent cell populations with upregulated glycolysis and acid resistance have a powerful growth advantage, which promotes unconstrained proliferation and invasion.

Why do cancers have high aerobic glycolysis

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Management guidelines for patients with thyroid nodules and differentiated thyroid cancer.

EMT Transition States during Tumor Progression and Metastasis.

Glycolysis is increased in cancer cells compared with normal cells. It has been shown that glucose enters cells via a family of five functional glucose transporters (GLUT). However, GLUT expression appears to be altered in human breast cancer, which may serve as a selective advantage and facilitate the metastatic potential of these cells. The relationship of GLUT isoform expression and breast cancer cell invasiveness has not been adequately addressed. Thus, the purpose of this study was to investigate whether an association exists between GLUT expression and human breast cancer cell invasiveness. Invasiveness of the human breast cancer lines MCF-7, MDA-MB-435 and MDA-MB-231 was measured using anin vitro assay and compared with cellular GLUT isoform expression, assessed by Western blot analysis and verified by immunohistochemistry in a poorly differentiated human ductal breast cancer. Cell surface GLUT-1 expression was associated with the invasive ability of MCF-7 (2.0 ± 0.02%), MDA-MB-435 (6.4 ±0.4%), and MDA-MB-231 (19.3 ± 2.0%). However, GLUT-2 and GLUT-5 were inversely associated with invasiveness; GLUT-3 expression was variable; and GLUT-4 was undetected. In a poorly differentiated human ductal breast cancer,in situ GLUT-1 staining was intense. GLUT-1 expression was associated with the in vitro invasive ability of human breast cancer cells which was validatedin situ. If this relationship is found to exist in a larger number of human breast cancer tissues, it may be possible to develop diagnostic and therapeutic strategies based on targeted GLUT isoform expression.

Role for Glucose Transporter 1 Protein in Human Breast Cancer

Pathology observational reports and experimental data suggest that keratin and vimentin intermediate filament (IF) coexpression in breast cancer confers a more aggressive “interconverted” phenotype, expressing both epithelial and mesenchymal markers. In this study, we extended previous observations by measuring the expression of keratin and vimentin, in relation to other selected biomarkers of disease progression, in postmenopausal women with breast cancer. Using immunohistochemical analysis of 54 archival, formalin-fixed, paraffin-embedded invasive breast cancers from a well-defined cohort, we examined relative IF (keratin and vimentin) expression in a semiquantitative fashion and compared these results with other biological markers and survival. By univariate analysis, we found that vimentin expression was inversely associated with keratin expression alone ( P = 0.0089) and directly related to histological grade ( P = 0.017), nuclear grade ( P = 0.027), Ki67 growth fraction ( P = 0.024), and epidermal growth factor receptor immunostaining ( P = 0.019). The relative expression of keratin and vimentin in approximately similar amounts characterized tumors with the poorest prognosis, as compared with keratin-high/vimentin-negative or keratin-low/vimentin-positive tumors. These latter two groups demonstrated similar Kaplan-Meier survival curves; the former group (keratin and vimentin in approximately similar amounts) demonstrated a poorer survival, with a hazard ratio of 2.1 (95% confidence interval, 0.5–9.6). These data suggest that relative keratin and vimentin IF expression is more indicative of prognosis and tumor phenotype than either IF marker detected independently.

https://clincancerres.aacrjournals.org/content/clincanres/5/10/2698.full.pdf

Association between Keratin and Vimentin Expression, Malignant Phenotype, and Survival in Postmenopausal Breast Cancer Patients

Objective. The prevalence of thyroid nodularity in children has been estimated to be 1.8%. The reported prevalence of specific diseases which comprise these nodules is conflicting as evidenced by a reported range of malignancy of 2 to 50% in solitary nodules. In order to better classify pediatric (<18 years old) thyroid disease and evaluate the utility of fine needle aspiration biopsy (FNAB) in this patient population, we retrospectively reviewed 66 FNABs from 64 thyroid nodules and 2 perithyroid lymph nodes from 57 patients. Methodology. Patients: The study was composed of 8 males and 49 females who ranged in age from 1 to 18 years old (mean=13.1). Design: Surgical and/or clinical follow-up was obtained in all patients. The 66 FNAB diagnoses were initially classified into specific diseases. However, for the purpose of this review, the cases were classified as: 3 insufficient, 51 benign, 8 suspicious, and 4 malignant. Results. There were no «false positives» and one «false negative» (a papillary carcinoma was misdiagnosed as a benign nodule). Overall, 10 patients (18%) had malignant thyroid lesions, including 8 papillary carcinomas and 2 follicular carcinomas. Benign diagnoses included benign nodule, cyst, lymphocytic thyroiditis, granulomatous thyroiditis, hyperplasia, and abscess. Conclusions. The prevalence of malignancy in pediatric patients with thyroid nodules was 18%. We conclude that, because of its high diagnostic accuracy and minimal invasiveness, FNAB is useful in the management of pediatric thyroid nodules

Pediatric Thyroid Nodules: Disease Demographics and Clinical Management as Determined by Fine Needle Aspiration Biopsy

Although cervical-vaginal telecytology is a promising tool, diagnostic accuracy has not been extensively evaluated. The authors examined the accuracy of five cytotechnologists who retrospectively reviewed 50 cervical-vaginal smears using the video monitor, and 2 months later, using the light microscope. Accuracy was expressed in terms of crude agreement with the original diagnosis and number of false positives (FPs) and false negatives (FNs). With a greater than one step difference as discrepant, the group crude agreement using the video monitor and the light microscope was 85.6% and 95.6%, respectively. The group number of FNs and FPs for the light microscope was 8 and 7, respectively, and for the video monitor was 34 and 7, respectively. There was a wide range of individual performance. We conclude that accuracy of telecytology is high, but less than that of light microscopy. The major reason for lower telecytologic accuracy was undercalling dysplasia.

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Telecytology: diagnostic accuracy in cervical-vaginal smears.

Histologic follow-up of the cervical-vaginal smear diagnosis of atypical glandular cells of undetermined significance (AGUS) shows a broad spectrum of clinically significant (preneoplastic or neoplastic) and benign lesions. There are few statistical studies that have attempted to separate these AGUS categories based on select cytologic criteria. The authors retrospectively reviewed 116 AGUS without concurrent squamous dysplasia smears (66 clinically significant and 50 benign lesions), and used logistic regression analysis to identify the cytologic criteria of irregular nuclear membranes, atypical single cells, and decreased cytoplasm as useful in separating clinically significant from benign lesions. Using contingency tables, these criteria in combination had a sensitivity 29% and a specificity of 94% in the diagnosis of clinically significant lesions. If any single criterion was present, the sensitivity and specificity were 100% and 28%, respectively. In conclusion, by using key cytologic criteria, a percentage of benign AGUS lesions can be separated from clinically significant AGUS lesions.

Patricia A. Thomas

Papers

Role for Glucose Transporter 1 Protein in Human Breast Cancer

Association between Keratin and Vimentin Expression, Malignant Phenotype, and Survival in Postmenopausal Breast Cancer Patients

Pediatric Thyroid Nodules: Disease Demographics and Clinical Management as Determined by Fine Needle Aspiration Biopsy

Telecytology: diagnostic accuracy in cervical-vaginal smears.

Atypical glandular cells of undetermined significance. Cytologic criteria to separate clinically significant from benign lesions.