Papillary Thyroid Carcinoma Disease Research Articles

Approach to risk stratification for papillary thyroid carcinoma based on molecular profiling: institutional analysis

Currently, treatment recommendations for papillary thyroid carcinoma are not based on the genetic background causing tumourigenesis. The aim of the present study was to correlate the mutational profile of papillary thyroid carcinoma with clinical parameters of tumour aggressiveness, to establish recommendations for risk-stratified surgical treatment. Papillary thyroid carcinoma tumour tissue of patients undergoing thyroid surgery at the University Medical Centre Mainz underwent analysis of BRAF, TERT promoter and RAS mutational status as well as potential RET and NTRK rearrangements. Mutation status was correlated with clinical course of disease. One hundred and seventy-one patients operated for papillary thyroid carcinoma were included. The median age was 48 years (range 8-85) and 69 per cent (118/171) of patients were females. One hundred and nine papillary thyroid carcinomas were BRAF-V600E mutant, 16 TERT promotor mutant and 12 RAS mutant; 12 papillary thyroid carcinomas harboured RET rearrangements and two papillary thyroid carcinomas showed NTRK rearrangements. TERT promoter mutant papillary thyroid carcinomas had a higher risk of distant metastasis (OR 51.3, 7.0 to 1048.2, P < 0.001) and radioiodine-refractory disease (OR 37.8, 9.9 to 169.5, P < 0.001). Concomitant BRAF and TERT promoter mutations increased the risk of radioiodine-refractory disease in papillary thyroid carcinoma (OR 21.7, 5.6 to 88.9, P < 0.001). RET rearrangements were associated with a higher count of tumour-affected lymph nodes (OR 7950.9, 233.7 to 270495.7, P < 0.001) but did not influence distant metastasis or radioiodine-refractory disease. Papillary thyroid carcinoma with concomitant BRAF-V600E and TERT promoter mutations demonstrated an aggressive course of disease, suggesting the need for a more extensive surgical strategy. RET rearrangement-positive papillary thyroid carcinoma did not affect the clinical outcome, potentially obviating the need for prophylactic lymphadenectomy.

Risk factors for persistent disease in papillary thyroid carcinoma with lymph node metastasis.

It is known that the presence of neck lymph node (LN) metastasis is correlated with persistent disease in papillary thyroid carcinoma (PTC) patients. After appropriate therapy, most patients become disease free, whereas some may still have persistent disease. The present study aimed to determine the potential variables affecting the clinical course of the disease and persistent disease patterns in PTC patients with LN metastasis. The study group included consecutive PTC patients with LN metastasis. Clinicopathological characteristics and persistent disease pattern during the follow-up period were examined to identify risk factors for persistent disease using univariate and multivariate analyses. At the end of a median follow-up of 84 months, 90 (69%) patients became disease free and 40 (31%) patients had persistent disease. Univariate analysis showed that male sex, older age at initial diagnose (≥45 years), larger tumor size (>4 cm), presence of lateral cervical LN metastasis, extrathyroidal invasion, and higher number of metastatic LN (≥10) were significant predictors for persistent disease. Multivariate analysis showed that extrathyroidal involvement, presence of lateral cervical LN metastasis, and older age at initial diagnosis (≥45 years) were independent predictors for persistent disease. Despite the presence of LN involvement, most patients may become disease free with therapy. Patients with extrathyroidal invasion, lateral cervical LN involvement, and those at least 45 years old at initial diagnosis are more likely to have persistent disease. However, disease control can be achieved with close clinical follow-up and therapy.

IL-4, IL-10 and high sensitivity-CRP as potential serum biomarkers of persistent/recurrent disease in papillary thyroid carcinoma with/without Hashimoto's thyroiditis

Objective. To investigate the potential role of interleukin 4 (IL-4), interleukin 10 (IL-10) and high-sensitivity C-reactive protein (hs-CRP) as serum biomarkers of persistent/recurrent disease in papillary thyroid carcinoma (PTC) with/without Hashimoto's thyroiditis (HT). Methods. Eighty consecutive patients (64 F/16 M, 43.2 ± 12.7 years) with PTC and 40 (37 F/3 M, 40.6 ± 12.3 years) with papillary thyroid carcinoma associated with Hashimoto's thyroiditis (PTC + HT) were evaluated before radioiodine therapy. A control group of 20 patients with HT without thyroid cancer (18 F/2 M, 47.3 ± 2.8 years) was included in the study for the comparison of cytokine levels. Results. No meaningful differences were found in clinical outcomes between PTC and PTC + HT groups (47.5% vs. 45% persistent/recurrent disease). Serum IL-4, IL-10 and hs-CRP levels were higher in patients with persistent/recurrent disease compared to those without recurrence (p < 0.001). IL-4, IL-10 and hs-CRP were also found in substantially higher concentrations in PTC + HT patients with persistent/recurrent disease than in patients with HT or PTC (with or without recurrence) (p < 0.01). Positive correlations were observed between IL-4, IL-10, hs-CRP and thyroglobulin (Tg) (r between 0.48 and 0.56, p < 0.005) or antithyroglobulin antibodies (TgAb) (r between 0.63 and 0.80, p < 0.002) in PTC and PTC + HT patients with persistent/recurrent disease. Conclusions. Increased levels of serum IL-4, IL-10 and hs-CRP are associated with persistent/recurrent disease in PTC and PTC + HT patients. Our results suggest that these biomarkers might be used to improve patient stratification according to the risk of recurrence, especially in patients with PTC + HT, where Tg levels are not reliable due to presence of TgAb.

Differential expression profiling of circulation microRNAs in PTC patients with non-131I and 131I-avid lungs metastases: a pilot study

IntroductionLoss of the ability to concentrate 131I is one of the important causes of radioiodine-refractory disease in papillary thyroid carcinoma (PTC). Recent advantages of serum microRNAs (miRNAs) open a new realm of possibilities for noninvasive diagnosis and prognosis of many cancers. The aim of the current study was to identify differential expression profiling of circulation miRNAs in PTC patients with non-131I and 131I-avid lungs metastases. MethodsThe expressions of miRNAs were examined using miRNA microarray chip. The most significantly changed miRNAs from microarray were verified by using qRT-PCR. The potential miRNAs regulating target genes and their preliminary biological functions were forecasted by Bioinformatic analysis. ResultsCompared to 131I-avid lung metastases, 13 kinds of significantly differential serum miRNAs including 5 upregulated miRNAs (miR-1249, miR-106a, miR-503, miR-34c-5p, miR-1281) and 8 downregulated miRNAs (miR-1915, miR-2861, miR-3196, miR-500, miR-572, miR-33b, miR-554, miR-18a) in PTC patients with non-131 I-avid lung metastases were identified. Bioinformatic analysis demonstrated that miR-106a was the core miRNA regulating 193 genes in the network. The results of validation confirmed the up-regulation of miR-106a in non-131I-avid lungs metastatic PTC patients. ConclusionDifferentially expressed serum miRNA profiles between PTC patients with non-131I and 131I-avid lungs metastases were analyzed. These findings in our present study could represent new clues for the diagnostic and therapeutic strategy in PTC patients with non-131I-avid metastatic disease.

On the Association Between Hashimoto's Thyroiditis and Papillary Thyroid Carcinoma: Looking 100 Years Back and, Hopefully, Fewer Years Ahead to Sort Out This Association

ThyroidVol. 23, No. 9 Letters to the EditorOn the Association Between Hashimoto's Thyroiditis and Papillary Thyroid Carcinoma: Looking 100 Years Back and, Hopefully, Fewer Years Ahead to Sort Out This AssociationSalvatore BenvengaSalvatore BenvengaDepartment of Clinical and Experimental Medicine; Master Program on Childhood, Adolescent and Women's Endocrine Health, University of Messina School of Medicine, Messina, Italy.Interdepartmental Program of Molecular & Clinical Endocrinology, and Women's Endocrine Health, University Hospital Policlinico G. Martino, Messina, Italy.Search for more papers by this authorPublished Online:9 Sep 2013https://doi.org/10.1089/thy.2013.0126AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"On the Association Between Hashimoto's Thyroiditis and Papillary Thyroid Carcinoma: Looking 100 Years Back and, Hopefully, Fewer Years Ahead to Sort Out This Association." , 23(9), pp. 1180–1181FiguresReferencesRelatedDetailsCited byThyroid cancer and thyroid autoimmune disease: A review of molecular aspects and clinical outcomesPathology - Research and Practice, Vol. 216, No. 9One-third of an Archivial Series of Papillary Thyroid Cancer (Years 2007–2015) Has Coexistent Chronic Lymphocytic Thyroiditis, Which Is Associated with a More Favorable Tumor-Node-Metastasis Staging1 December 2017 | Frontiers in Endocrinology, Vol. 8The micropapillary/hobnail variant of papillary thyroid carcinoma: A review of series described in the literature compared to a series from one southern Italy pathology institution28 November 2016 | Reviews in Endocrine and Metabolic Disorders, Vol. 17, No. 4Editorial: A journey from brain to muscle across the thyroid continent7 March 2017 | Reviews in Endocrine and Metabolic Disorders, Vol. 17, No. 4Thyroid nodules and thyroid autoimmunity in the context of environmental pollution29 January 2016 | Reviews in Endocrine and Metabolic Disorders, Vol. 16, No. 4IL-4, IL-10 and high sensitivity-CRP as potential serum biomarkers of persistent/recurrent disease in papillary thyroid carcinoma with/without Hashimoto's thyroiditis17 July 2015 | Scandinavian Journal of Clinical and Laboratory Investigation, Vol. 75, No. 7Clinical Aggressiveness and Long-Term Outcome in Patients with Papillary Thyroid Cancer and Circulating Anti-Thyroglobulin Autoantibodies Cosimo Durante, Sara Tognini, Teresa Montesano, Fabio Orlandi, Massimo Torlontano, Efisio Puxeddu, Marco Attard, Giuseppe Costante, Salvatore Tumino, Domenico Meringolo, Rocco Bruno, Fabiana Trulli, Maria Toteda, Adriano Redler, Giuseppe Ronga, Sebastiano Filetti, Fabio Monzani, and 3 July 2014 | Thyroid, Vol. 24, No. 7 Volume 23Issue 9Sep 2013 InformationCopyright 2013, Mary Ann Liebert, Inc.To cite this article:Salvatore Benvenga.On the Association Between Hashimoto's Thyroiditis and Papillary Thyroid Carcinoma: Looking 100 Years Back and, Hopefully, Fewer Years Ahead to Sort Out This Association.Thyroid.Sep 2013.1180-1181.http://doi.org/10.1089/thy.2013.0126Published in Volume: 23 Issue 9: September 9, 2013Online Ahead of Editing: April 22, 2013PDF download

BRAF Mutation Analysis of Fine-Needle Aspiration Biopsies of Papillary Thyroid Carcinoma: Impact on Diagnosis and Prognosis

Objective: The BRAF V600E mutation has been associated with aggressive disease in papillary thyroid carcinoma (PTC). Molecular testing has been proposed as a useful adjunct to cytology in the diagnosis of malignancy and for tailoring clinical management. The aims of our study were to evaluate the BRAF mutational status using archived fine-needle aspiration biopsy (FNAB) material from patients with long-term follow-up and to correlate it with the original cytology diagnosis, clinicopathological stage at surgery, and prognosis. Study Design: FNAB material from 52 cases of PTC, with a mean follow-up of 8.4 years, was used in this study. DNA was extracted from archival cytology slides. Mutation analysis was performed by standard sequencing and locked nucleic acid-PCR/sequencing. Results: The BRAF V600E mutation was present in 46% of cases, but it was absent in all FNABs diagnosed originally as atypical and in 14 of 17 suspicious cases. Recurrence was significantly more frequent (p = 0.006) in cases with BRAF mutations and 54% of these cases presented with stage 2 or higher. Conclusion: The BRAF V600E mutation is associated with a higher pathological stage at surgery and a higher rate of recurrence. BRAF mutation analysis did not provide a significant increase in the accuracy of thyroid FNABs diagnosed as suspicious or atypical in our institution.

Utility of Computed Tomography in the Detection of Subclinical Nodal Disease in Papillary Thyroid Carcinoma

To characterize the ability of computed tomography (CT) to identify subclinical cervical metastatic disease in papillary thyroid carcinoma (PTC). Retrospective review. Tertiary academic center. Consecutive patients undergoing neck dissection for PTC between July 1, 2004, and July 1, 2006. Preoperative CT scans were reevaluated in a blinded fashion by a single head and neck radiologist. Positive criteria included node with size larger than 10 mm, round shape, calcification, cystic character, or abnormal enhancement. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated separately for central compartment (level VI) and lateral compartment (levels III and IV) dissections. One hundred four patients underwent selective neck dissection for PTC during the study period. Forty-three patients had disease that involved primary lymphadenectomy at the time of thyroidectomy, and 61 had persistent or recurrent disease. There were 111 lateral compartment dissections and 145 central compartment dissections. The overall sensitivity was 59% for both the central and lateral compartments, and the specificity was 76% and 71%, respectively. The PPV and NPV were 84% and 47% for the central compartment and 73% and 57% for the lateral compartment, respectively. Computed tomography has a limited capability to identify subclinical metastatic cervical disease in PTC, with a sensitivity near 60% and an NPV near 50%. Sole reliance on CT findings will miss a significant portion of disease likely because of the high incidence of microscopic foci. However, using strict criteria, a positive finding on a CT scan provides useful information because it predicts with a fairly high assurance that disease will in fact be found in a specific compartment during surgical dissection.

Inflammatory Diseases of the Lung Causing False-Positive 131Iodine Whole Body Scans in the Evaluation of Papillary Thyroid Carcinoma: Two Case Reports

The ¹³¹I whole body scan is commonly used to establish the presence of metastatic disease in papillary thyroid carcinoma. False-positive scans are rare, but have been reported. We present two cases of aberrant uptake of radioiodine after thyroidectomy and ¹³¹I ablation due to inflammatory conditions of the lung, aspergilloma, and respiratory bronchiolitis.