Assessment of inflammatory parameters as predictive markers for malignancy in thyroid nodules: a study on the correlation with Bethesda classification.

OBJECTIVE: The study aimed to assess the predictive significance of inflammatory parameters as potential markers for malignancy in individuals with thyroid nodules. METHOD: Nine hundred and ninety-one patients with thyroid nodules who had undergone thyroid fine-needle aspiration biopsy were included and classified according to the Bethesda system. Neutrophil lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) values obtained from hemogram parameters were determined for each patient. The study examined the correlation between the Bethesda classification and NLR/SII levels. In addition, a comparison was made between the inflammatory parameters of the benign and malignant Bethesda groups. RESULTS: Five hundred and seventy-three patients were classified as Bethesda 2 (benign), 34 as Bethesda 6 (malignant). A correlation was observed between the Bethesda classification and NLR and SII levels (r: 0.230, p < 0.001; r: 0.207 p < 0.001, respectively). NLR and SII values were significantly higher in the malignant group (p < 0.001). The cutoff value for SII in predicting benign and malignant thyroid nodules was 489.86 × 103/mm3 with a sensitivity of 88.2% and a specificity of 63.7%. The cutoff value for NLR for the same prediction was 2.06 with a sensitivity of 82.4% and a specificity of 83.4%. CONCLUSIONS: The findings of this study indicate that SII and NLR may be valuable prognostic markers for predicting the malignancy of thyroid nodules.

OBJETIVO: Evaluar parámetros inflamatorios como posibles marcadores de malignidad en individuos con nódulos tiroideos. MÉTODO: Se incluyeron 991 pacientes con nódulos tiroideos que se sometieron a biopsia por aspiración con aguja fina y se clasificaron según el sistema de Bethesda. Se determinaron los valores de la relación neutrófilo-linfocito (NLR) y el índice de inflamación inmunitaria sistémica (SII). El estudio exploró la correlación entre la clasificación de Bethesda y los valores de NLR/SII, y comparó los parámetros inflamatorios de los grupos benignos y malignos de Bethesda. RESULTADOS: Se clasificaron 573 pacientes como Bethesda 2 (benigno) y 34 como Bethesda 6 (maligno). Se observó una correlación entre la clasificación de Bethesda y los valores de NLR y SII (r: 0.230; r: 0.207). Los valores de NLR y SII fueron mayores en el grupo maligno (p < 0.001). El valor de corte para SII en la predicción de nódulos tiroideos benignos y malignos fue de 489.86 × 103/mm3, con una sensibilidad del 88.2% y una especificidad del 63.7%; para NLR fue de 2.06, con una sensibilidad del 82.4% y una especificidad del 83.4%. CONCLUSIONES: El SII y el NLR pueden ser valiosos marcadores pronósticos para predecir la malignidad de los nódulos tiroideos.

[Tumors of the thyroid gland. Proposal for the management and study of samples from patients with thyroid neoplasms]. / Tumores de la glándula tiroides. Propuesta para el manejo y estudio de las muestras de pacientes con neoplasias tiroideas.

The recent changes in the classification and staging of thyroid tumors have arisen from the need to provide an adequate response to the exponential increase of thyroid cancer, which, however, has not been accompanied by an increase in mortality. These changes pretend to reduce overdiagnoses of malignancy, unnecessary treatment, side effects as well as cost for the health system. To this end, this article reviews recommendations for the management of thyroid surgical pathology samples with emphasis on the new terminology of the WHO classification. The basic criteria for the diagnosis of malignancy in well-differentiated thyroid carcinomas are reviewed and the criteria for NIFTP (non-invasive follicular tumor with papillary-like nuclear features) diagnosis are updated. Recommendations for the elaboration of the pathological report are also included.

Ultrasound-guided fine needle aspiration of thyroid nodules with on-site cytological examination: Diagnostic efficacy, prevalence, and factors predicting for Bethesda category I results. / Punción-aspiración con aguja fina ecoguiada de nódulos tiroideos con valoración citológica in situ: eficacia diagnóstica, prevalencia y factores predictores de los resultados de categoría Bethesda I.

BACKGROUND AND OBJECTIVE: Ultrasound-guided fine needle aspiration of thyroid nodules with on-site cytological examination may decrease the number of Bethesda categoryI cytologies. The study objective was to evaluate our second-year experience with this procedure to analyze diagnostic efficacy, prevalence, and factors predicting for Bethesda categoryI results. PATIENTS AND METHOD: A retrospective study was conducted of 279 nodules from 233 patients. Ultrasound -guided fine needle aspiration was performed according to the 2015 criteria of the American Thyroid Association. A specimen of each aspiration was air-fixed on site before Diff-Quik staining and microscopic examination to assess its suitability; otherwise, nodule aspiration was repeated up to 5times. Diagnostic efficacy was assessed based on sensitivity and specificity on the cytological categories BethesdaII and BethesdaVI. RESULTS: Diagnostic sensitivity and specificity were both 100%, 5.4% Bethesda categoryI results were obtained, and variables independently associated were age (4.7% increase per year of life) and nodule volume (2.3% increase per each 1mL of volume). CONCLUSIONS: Ultrasound-guided fine needle aspiration of thyroid nodules with on-site cytological examination allows for a high diagnostic efficacy and has been shown to be a highly relevant procedure because it has a very low rate of cytological results of Bethesda categoryI, whose risk has been higher in older subjects and with larger nodules.

Clinical Assessment and Risk Stratification in Differentiated Thyroid Cancer.

Thyroid cancer management is rapidly evolving to a personalized management approach. Risk stratification systems are designed to assist in personalized management. Differentiating patients who may benefit from aggressive therapy and intense follow-up as opposed to those who can be successfully treated with minimalized initial management options and follow-up is crucial to the development of the right treatment plan for the right patient in order to optimize initial therapy and follow-up testing. This article aims to describe and discuss the risk stratification systems currently recommended for differentiated thyroid cancer.

The Ethical Implications of the Reclassification of Noninvasive Follicular Variant Papillary Thyroid Carcinoma.

BACKGROUND: Several studies have highlighted the lack of consensus in the diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC). An international multidisciplinary panel to address the controversy was assembled at the annual meeting of the Endocrine Pathology Society in March of 2015, leading to the recent publication reclassifying encapsulated (or noninvasive) FVPTC (EFVPTC) as a benign neoplasm. Does this change in histologic taxonomy warrant a change in clinical practice, and how should it affect those who have been given this diagnosis in the past? We consider the financial and psychological impact of this reclassification and discuss the ethical, legal, and practical issues involved with sharing this information with the patients who are affected. SUMMARY: The total direct and indirect cost of thyroid cancer surveillance in patients is significant. High levels of clinically relevant distress affect up to 43% of patients with papillary thyroid carcinoma, as estimated by the Distress Thermometer developed by the National Comprehensive Cancer Network for detecting distress in cancer patients. Although there are currently no legal opinions that establish a precedent for recontacting patients whose clinical status is altered by a change in nomenclature, the prudent course would be to attend to the requirements of medical ethics. CONCLUSION: Informing patients with a previous diagnosis of EFVPTC that the disease has been reclassified as benign is expected to have a dramatic effect on their surveillance needs and to alleviate the psychological impact of living with a diagnosis of cancer. It is important to re-evaluate the pathologic slides of those patients at risk to ensure that the invasive nature of the tumor is comprehensively evaluated before notifying a patient of a change in diagnosis. The availability of the entire tumor for evaluation of the capsule may prove to be a challenge for a portion of the population at risk. We believe that it is the clinician's professional duty to make a sincere and reasonable effort to convey the information to the affected patients. We also believe that the cost savings with respect to the need for additional surgery, radioactive iodine, and rigorous surveillance associated with a misinterpretation of the biology of the diagnosis of EFVPTC in less experienced hands will likely more than offset the cost incurred in histologic review and patient notification.

The Effect of Implementing Gene Expression Classifier on Outcomes of Thyroid Nodules with Indeterminate Cytology.

Thyroid nodules are classified into six cytological categories under the Bethesda classification system. Two of these categories, atypical of undetermined significance (AUS) and suspicious for a follicular neoplasm (SFN), are further labeled as "indeterminate" diagnosis. Starting in June, 2012, Kansas University-Wichita Endocrine clinic implemented Afirma® Gene Expression Classifier (AGEC) to evaluate the need for surgical resection of thyroid nodules in patients with an indeterminate diagnosis. Electronic medical records of patients who underwent thyroid nodule fine-needle aspiration from 2004-2014 were reviewed. The aim of this study was to find whether implementing AGEC was associated with decreased surgical recommendation rate, decreased cost, and increased incidence of thyroid malignancy diagnosed by surgery in patients with indeterminate diagnosis. A total of 299 consecutive patients' charts were screened. Sixty-one (20 %) patients had an indeterminate diagnosis. Out of these, 27 (44 %) patients underwent evaluation before and 34 (56 %) patients underwent evaluation after AGEC implementation, respectively. Surgical recommendation for patients with indeterminate finding decreased from 81.5 to 50 % (p = 0.01) after AGEC implementation. Surgical pathology was read as malignant in 20 and 85.7 % (p < 0.01) of patients before and after AGEC implementation, respectively. Primary cost-benefit estimate showed implementing AGEC has saved $1048/patient in medical evaluation and initial management of patients with indeterminate diagnosis. AGEC implementation has decreased the number of surgical recommendations, has lowered financial burden, and has increased incidence of thyroid malignancy diagnosed by surgical pathology in patients with indeterminate diagnosis of thyroid nodules.

Pitfalls in the Cytological Assessment of Thyroid Nodules.

Fine needle aspiration of thyroid has been used for years in a multidisciplinary approach, to diagnose different entities, in preventing over or under treatment of thyroid nodules. The widespread use of this methodology can be confirmed if "thyroid fine needle aspiration" is searched on PubMed, which results in over 5000 papers. In this manuscript, we aimed to focus on pitfalls in the evaluation of thyroid aspirations, covering cystic, inflammatory lesions, follicular lesions, oncocytic lesions, papillary carcinoma, and medullary carcinoma of thyroid.

TIRADS for sonographic assessment of hypofunctioning and indifferent thyroid nodules.

AIM: To test the feasibility of the Thyroid Imaging Reporting And Data System (TIRADS) according to Horvath and Kwak for the assessment of thyroid nodules. PATIENTS, METHOD: Retrospective analysis of patients with thyroid nodules applying the following inclusion criteria: B-mode-ultrasound, surgery and histological results. Thyroid nodules were classified as TIRADS 2, 3, 4A, 4B, 4C, 5 and 6. RESULTS: A total of 172 patients were included (133 women, 48 ± 13 years, 39 men, 49 ± 11 years) with 222 thyroid nodules (24.9 ± 11.5 mm). Final histological diagnosis revealed 203 benign nodules (91%) and 19 malignant nodules (9%; 18 papillary thyroid carcinoma, PTC, and one medullary thyroid carcinoma, MTC). One hundred and sixty thyroid nodules were hypofunctioning in 99mTc-pertechnetate-scintigraphy, 14 nodules were hyperfunctioning and 46 nodules were classified as indifferent. In two cases with small carcinoma < 1 cm 99mTc-pertechnetate-scintigraphy was not performed. According to Horvath, the prevalence of malignancy was 6.7% in TIRADS 2, 0% in 3, 1.9% in 4A, 33% in 4B, 12.5% in 5 and 100% in 6; 73 nodules (39%) were not clearly classifiable, including 3 carcinoma (4.1%). According to Kwak, the prevalence of malignancy was 6.9% in TIRADS 2, 0% in 3, 2% in 4A, 4.1% in 4B, 23.1% in 4C, and 100% in 5 and 6, respectively. Notably, in the subgroup of hot nodules, 11 (79%) were graded as TIRADS 4A or higher, and thus advisable for fine-needle aspiration biopsy in both TIRADS. CONCLUSION: The TIRADS described by Horvath is not practicable due to numerous unclassifiable nodules. The revised TIRADS published by Kwak is feasible and suitable to assess the prevalence of malignancy, but it cannot replace scintigraphic imaging. Fine-needle-biopsy is not necessary in nodules categorized as (K)TIRADS 3, 4A and 5.

Risk-adapted management of papillary thyroid carcinoma according to our own risk group classification system: is thyroid lobectomy the treatment of choice for low-risk patients?

BACKGROUND: Our original system for risk group classification for predicting cause-specific death from papillary thyroid carcinoma (PTC) defined patients with distant metastasis and older patients (≥ 50 years) with either massive extrathyroidal extension or large (≥ 3 cm) lymph node metastasis as high risk; all others are low risk. For unilateral, low-risk PTC, the extent of thyroidectomy (less-than-total thyroidectomy vs total or near-total thyroidectomy) has been determined based on the choice of the patient since 2005. PATIENTS: Of 1,187 patients who underwent initial thyroidectomy for PTC (tumor size [T] >1 cm) between 1993 and 2010, 967 (82%) were classified as low risk. Among low-risk patients, 791 (82%) underwent less than total thyroidectomy. RESULTS: The 10-year cause-specific survival and disease-free survival rates did not differ between patients who underwent total thyroidectomy versus less than total thyroidectomy (cause-specific survival, 99% vs 99% [P = .61]; disease-free survival, 91% vs 87% [P = .90]). Age ≥ 60 years, T ≥ 3 cm, and lymph node metastases >3 cm represented significant risk factors for distant recurrence. CONCLUSION: The favorable overall survival of low-risk patients, regardless of the extent of thyroidectomy, supports patient autonomy in treatment-related decision making. Low-risk patients possessing risk factors for distant recurrence would be likely to benefit from total thyroidectomy followed by radioactive iodine.

High default rate in thyroid cancer management in Ibadan, Nigeria: a need for health insurance.

BACKGROUND: Differentiated thyroid cancer is a potentially curable disease provided there is early diagnosis and full compliance with management modalities. This however becomes a problem in a resource poor environment where most patients pay out of pocket resulting in poor compliance and inability to access standard care due to poverty. This retrospective study was carried out to evaluate the percentage of patients that could afford the cost of care in a premier nuclear medicine facility of a tertiary centre. PATIENTS, MATERIAL AND METHOD: A total 56 patients with differentiated thyroid cancer managed since the inception of the Nuclear Medicine Department, University College Hospital from June 2006 to March 2010 were included in the study. Socioeconomic status of the patients and the affordability of the nuclear medicine procedure for differentiated thyroid cancer post thyroidectomy were evaluated. RESULT: A total of 20 out of 56 (35.7%) patients had total thyroidectomy at presentation, while, 36 had subtotal thyroidectomy. The commonest type of thyroid malignancy was papillary thyroid cancer (51.8%), while follicular cancer accounted for 41.1%. Medullary and Anaplastic thyroid cancers were the least common. Majority of the patients evaluated were within the income bracket of 10,000-30,000 naira ($67- $200) per month). The average cost of management of thyroid cancer post total thyroidectomy was $2500 (N375 000.00) at this centre. Twenty one out of 56 patients (37.5%) could afford the $300 cost of diagnostic whole body iodine scan while only 16 patients out 21 (28.6%) could afford the ($1200) cost of radioactive iodine treatment. CONCLUSION: With average cost of management of management of thyroid cancer beyond the yearly income of majority of the patients studied, there is need for a comprehensive health insurance policy to make accessibility of care of this potentially curable disease available to most Nigerians.

Cost-effective and non-invasive automated benign and malignant thyroid lesion classification in 3D contrast-enhanced ultrasound using combination of wavelets and textures: a class of ThyroScan™ algorithms.

Ultrasound has great potential to aid in the differential diagnosis of malignant and benign thyroid lesions, but interpretative pitfalls exist and the accuracy is still poor. To overcome these difficulties, we developed and analyzed a range of knowledge representation techniques, which are a class of ThyroScan™ algorithms from Global Biomedical Technologies Inc., California, USA, for automatic classification of benign and malignant thyroid lesions. The analysis is based on data obtained from twenty nodules (ten benign and ten malignant) taken from 3D contrast-enhanced ultrasound images. Fine needle aspiration biopsy and histology confirmed malignancy. Discrete Wavelet Transform (DWT) and texture algorithms are used to extract relevant features from the thyroid images. The resulting feature vectors are fed to three different classifiers: K-Nearest Neighbor (K-NN), Probabilistic Neural Network (PNN), and Decision Tree (DeTr). The performance of these classifiers is compared using Receiver Operating Characteristic (ROC) curves. Our results show that combination of DWT and texture features coupled with K-NN resulted in good performance measures with the area of under the ROC curve of 0.987, a classification accuracy of 98.9%, a sensitivity of 98%, and a specificity of 99.8%. Finally, we have proposed a novel integrated index called Thyroid Malignancy Index (TMI), which is made up of texture features, to diagnose benign or malignant nodules using just one index. We hope that this TMI will help clinicians in a more objective detection of benign and malignant thyroid lesions.

Objective differential classification of thyroid lesions by nuclear quantitative assessment.

Quantitative nuclear parameters estimated by morphometric and stereological methods in combination with discriminant analysis were used in order to evaluate the diagnostic efficiency of thyroid lesions. This study includes 55 patients with thyroid pathology. Samples of follicular adenomas, follicular carcinomas, and papillary carcinomas were examined by image analysis to obtain size and form nuclear parameters. Stepwise discriminant analyses were performed. There was an increase in nuclear size from follicular adenomas to follicular carcinomas, and a greater increase from follicular carcinomas to papillary carcinomas. The increase was more significant when the three-dimensional estimates of the volume-weighted mean nuclear volume were assessed. No significant differences between follicular adenomas and follicular carcinomas were found with respect to the nuclear form factors, however, a significant increase in nuclear elongation and irregularity was registered between follicular and papillary tumors (p < 0.01). The overall accuracy rate of discrimination was 75% when the three lesions were included in the analysis, with an efficiency of 85% for papillary carcinoma samples. These percentages increased when two lesion discrimination was performed. The worst discrimination (69% of efficiency) was found between follicular adenomas and follicular carcinomas.

Well differentiated follicular neoplasms of the thyroid: reproducibility and validity of a 'decision tree' classification based on nucleolar and karyometric features.

This study was conducted on fine-needle aspirates of well differentiated follicular neoplasms of the thyroid. A 'decision tree' classification based on the percentage of nucleolated nuclei, percentage of nuclei with two or more nucleoli and mean major nuclear diameter was adopted. We observed that the reproducibility and the validity of the follicular adenoma vs follicular carcinoma discrimination are greater than in the subjective evaluation. Moreover, similar classification results were obtained when measurements were performed either with a fully automated image analysis system or with semiautomatic or manual instrumentation. As for reproducibility of the inter-instrument comparisons, the k statistic values ranged from 0.85 to 1.00 (mean value 0.90, that is, an 'almost perfect' degree of agreement); in the subjective evaluations, the inter-observer comparisons showed values ranging from 0.20 to 0.56 (mean value 0.37, that is, 'fair'). In the decision tree classification, feature value thresholds were selected in order to have specificity of 100% and the predictive value of a positive result (carcinoma) of 100%; accuracy was 87% (range 86-89%), sensitivity 74% (71-79%), the predictive value of a negative result (adenoma) 79% (78-82%). In the subjective evaluation the values were as follows: accuracy 67% (64-71%), sensitivity 57% (50-64%), specificity 77% (71-79%), predictive value of a negative result (adenoma) 64% (61-69%), predictive value of a positive result (carcinoma) 71% (67-75%). The conclusion is that, by using a routine microscope equipped with a micrometer, the preoperative diagnosis of follicular carcinoma from smears can be formulated with a high degree of certainty.