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PubMed1995

Management of papillary thyroid cancer.

Papillary thyroid cancer is predominantly a sporadic disease that usually presents as an asymptomatic thyroid mass in a euthyroid patient. Irradiation to the neck during childhood significantly increases the subsequent risk of this cancer; the prognosis for radiation-related cancers is similar to spontaneous cases. Physical examination, thyroid scanning and ultrasound, and fine-needle aspiration are used to differentiate between benign lesions and papillary thyroid cancer. Near-total thyroidectomy with postoperative radioiodine ablation is currently advocated for most patients, and has excellent results with regard to survival. In children, papillary thyroid cancer often presents with extensive regional disease as well as diffuse lung metastases. Surgery and radioiodine are very effective in such cases, and survival remains excellent. As late recurrences may occur, patients require regular long-term follow-up regardless of the extent of initial disease.

Adolescent↗
PubMed2000

Papillary thyroid cancer.

Papillary thyroid cancer is the most common neoplasm of the thyroid gland. Surgical resection is the cornerstone of therapy. There is controversy regarding the extent of resection, ranging from thyroid lobectomy plus isthmusectomy to total thyroidectomy, but in experienced hands total thyroidectomy has many significant advantages over a lesser operation. Nonoperative therapy has no role as primary therapy for papillary thyroid cancer, but can be used in conjunction with surgery to improve outcome. Radioiodine in patients who have received total thyroidectomy can be used to identify residual occult tumor, recurrence, and metastasis, and can also be used to ablate the neoplasm, resulting in a substantial cure rate. Thyroid hormone is needed as replacement after total thyroidectomy, but can also be given as thyroid-stimulating hormone suppression, which may have an adjunctive benefit after resection.

Carcinoma, Papillary↗
PubMed2001

Macroscopic extranodal invasion is a risk factor for tumor recurrence in papillary thyroid cancer.

Papillary thyroid cancer patients, upon whom curative operation was performed, were investigated to clarify whether or not macroscopic extranodal invasion is a risk factor for recurrence. They were divided into three groups: group A, patients whose primary tumor showed extrathyroidal invasion (n=31); group B, those whose metastatic lymph nodes showed extranodal invasion (n=6); group C, those who showed both extrathyroidal and extranodal invasion (n=9). Recurrence was significantly higher in groups B and C than in group A (P<0.05). It was concluded that macroscopic extranodal invasion to the adjacent structures was a risk factor for recurrence in patients with papillary thyroid cancer.

Adult↗
PubMed2005

Favorable surgical results in 433 elderly patients with papillary thyroid cancer.

Papillary thyroid cancer (PTC) has a good prognosis among patients younger than 45 years old, but the prognosis in elder is worse and treatment strategy is not well established. We retrospectively analyzed the clinical features and outcomes of 433 patients with PTC aged 70 years or older. The patients consisted of three groups: group A (n = 327); patients receiving surgical treatment, group B (n = 51); patients with microcancer (maximal diameter, < or = 1.0 cm) who did not undergo surgical treatment, group C (n = 55); patients in whom surgery was contraindicated due to age, high surgical risk or complication by other illnesses. In group A, the mean tumor size was 2.6 +/- 1.5 cm, and 218 patients (66.7%) had pathologically confirmed lymph node metastasis; 110 patients (33.6%) had extrathyroidal invasion. The 5- and 10-year overall survival rates (OSR) in group A were 97.2% and 85%, respectively, which was significantly higher than the 5-year OSR in group C (62.6%). The 5- and 10-year disease-specific survival rates (DSSR) in group A were 98.5% and 91.3%, respectively, which was also significantly higher than the 5-year DSSR in group C (81.8%). Although the patients in group B did not receive any treatment, none of them demonstrated cause-specific death or progression of disease. Papillary thyroid cancer in elderly patients, except for microcancers, may be biologically aggressive. Thus surgery is recommended for these patients, if their general status is judged able to tolerate the stress of anesthesia and surgery.

Aged↗
PubMed2006

Papillary thyroid cancer.

Papillary thyroid cancer (PTC), the most common thyroid malignancy, is associated with an excellent prognosis. Overall survival is more than 90%. The first-line treatment is surgical excision, and although the debate continues as to whether a total thyroidectomy or thyroid lobectomy should be recommended, most patients at the University of California, San Francisco are treated with a total thyroidectomy. Not only has this been shown to be superior for overall survival in select patient populations, but local recurrence is also significantly lower with this approach. Total thyroidectomy also optimizes the adjuvant treatment options that are unique to "differentiated" thyroid cancer because these malignant cells retain many of the features of the native thyroid follicular cell. These cellular features are used for specialized investigations and treatment options in patients with PTC. For example, PTC cells retain the ability to produce thyroglobulin, to be stimulated by thyroid-stimulating hormone (TSH), and to take up iodine. These features are vital and separate differentiated thyroid cancer from other epithelial malignancies because such features can be used in clinical follow-up (monitoring serum thyroglobulin levels, whole body radioactive iodine scans) and in the treatment of patients with PTC (TSH suppression, radioactive iodine ablation of thyroid remnant, local recurrences, and regional or distant metastases). In summary, the wide array of treatment options for patients with PTC includes surgery, radioactive iodine, thyroid hormone suppression of TSH, external beam radiation (less commonly), and rarely, chemotherapy. This continues to be an area of exciting research for emerging therapy, much of which concentrates on enhancing or re-establishing the differentiated features of the thyroid cancer cell, in an effort to optimize the adjuvant treatment options. The treatment options that are chosen depend on patient factors, disease factors, and the decisions of the patient and treatment team.

Antineoplastic Agents↗
PubMed2005

Immunohistochemical expression of Bcl-2, Ki-67, and p21 in patients with papillary thyroid cancer.

Papillary thyroid cancer (PTC) is a slow-growing tumor with a favorable outcome. Still, some low-risk patients develop local or distant metastases and eventually die from their disease. Many molecular markers are involved in proliferation and apoptosis, including Bcl-2, Ki-67, and p21. Because age over 45 is the most important determinant of a poor survival, we analyzed whether the expression of these tumor proliferation markers differs between young and older PTC patients. Our study comprised 108 PTC patients retrospectively selected by age, i.e. those younger than 35 or older than 55 at diagnosis. Formalin-fixed, paraffin-embedded archival tissue blocks were analyzed for Bcl-2, Ki-67, and p21 protein expression by immunohistochemistry. We showed that expression of Ki-67 increases significantly with age, indicating that tumors in older patients may grow faster. This higher proliferative activity may explain the worse prognosis in these patients. Expression of p21 was higher in large tumors and in tumors extending beyond the thyroid capsule. Expression of Bcl-2 did not correlate with clinical parameters.

Adult↗
PubMed2026

Protective TGF&#x3b2;2/SMAD3 axis identified by TWAS in papillary thyroid cancer.

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Although generally indolent, a subset shows aggressive behaviour. Furthermore, the genetic heterogeneity of PTC is not fully explained by known driver mutations, underscoring the need to identify additional susceptibility genes and regulatory mechanisms. To identify additional susceptibility genes and regulatory mechanisms, we integrated transcriptome-wide association studies (TWAS) with summary-data-based Mendelian randomisation (SMR), joint/conditional testing (JCT), and colocalisation analyses across multiple independent cohorts, followed by heterogeneity in dependent instruments (HEIDI) test. Gene prioritisation analyses consistently highlighted TGFB2 and SMAD3 as candidate susceptibility genes for PTC, with SMR supporting putative protective effects. Besides, GEPIA confirmed the positive correlation between TGFB2 and SMAD3 expression in TCGA-THCA. Functional experiments in TPC-1 cells showed that TGF&#x3b2;2 treatment inhibited cell proliferation and migration, induced apoptosis, and resulted in G0/G1 cell-cycle arrest, accompanied by increased SMAD3 phosphorylation, suggesting activation of canonical TGF&#x3b2; signalling. Collectively, these findings bridge population-based genetic inference with mechanistic validation and suggest convergent evidence supporting a tumour-suppressive role of the TGF&#x3b2;2/SMAD3 axis in PTC.

Humans↗
PubMed2004

Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer.

Papillary thyroid carcinoma (PTC) is associated with RET and NTRK1 rearrangements and BRAF mutations. A series of 60 PTCs collected in a single center from Italian patients were histologically re-examined and subclassified as well differentiated or tall cell variant. The sample collection was analysed for the presence of all the reported PTC-associated genetic alterations through DNA or cDNA amplification, followed by automated sequencing. The analysis of exons 11 and 15 of BRAF gene revealed the T1796A (V599E) mutation in 32% of cases, and this alteration is significantly associated with PTC tall cell variant. Oncogenic rearrangements of RET and NTRK1 receptors were found in 33 and 5% of cases, respectively. No Ras mutations were detected. Overall, genetic alterations were detected in two-thirds of samples, and in no single case more than one mutational event was found simultaneously. Gene expression profiling of a subset of 31 tumors performed using cDNA microarray chips showed no strong differences in global gene expression among the different cases. However, a supervised analysis of the obtained data identified a subset of genes differentially expressed in tumors carrying BRAF mutation or RTK rearrangement.

Adenocarcinoma, Papillary↗
PubMed2001

Medullary thyroid cancer, papillary thyroid microcarcinoma and Graves' disease: an unusual clinical coexistence.

We describe the unusual case of a Caucasian woman who had a diagnosis of medullary thyroid cancer and papillary microcarcinoma 5 years after a diagnosis of Graves' disease. The patient came to our observation for recurrence of hyperthyroidism. An ultrasound scan revealed diffuse thyroid enlargement with a nodule, recently increased in size. The serum CT and carcinoembrional antigen were elevated, and the fine-needle aspiration cytology with immunocytochemical analysis for CT was suggestive for medullary thyroid carcinoma. The nodular lesion showed intense 111In-pentetreotide uptake, whereas total body scintigraphy with the same tracer and with Thallium-201, 99mTc (V) dimercaptosuccinic acid was negative for lymph node and distant metastasis. The histological examination of thyroidectomy specimens confirmed the diagnosis of medullary thyroid cancer, showing a lymphocytic intratumoral infiltration. The histological analysis of the controlateral lobe showed an occult papillary microcarcinoma. Medullary thyroid carcinoma and papillary microcarcinoma showed intense staining with policlonal anti-RET antibodies, although genetic analysis was negative for RET mutations most frequently involved in familial and sporadic medullary thyroid carcinomas. Possible implications about the coexistence of the 3 thyroid diseases are discussed.

Adult↗
PubMed2005

Papillary thyroid cancer: medical management and follow-up.

The incidence of epithelial derived thyroid cancer (papillary thyroid cancer and follicular thyroid cancer, known collectively as differentiated thyroid cancer) is rising. About 80% of patients with thyroid cancer have PTC and are best treated with thyroidectomy and functional lymph node dissection, followed by radioiodine ablation or therapy and performance of a posttreatment whole-body scan, followed by thyroid stimulating hormone (TSH) suppression. One year after radioiodine administration, the use of sensitive thyroglobulin (Tg) assays can separate the vast majority of patients with persistent disease from those who are free of disease and unlikely to have recurrent disease all without the need for repeat whole-body radioiodine imaging. Patients with detectable serum Tg during TSH suppression (Tg-on) or Tg that rises above 2 ng/mL after TSH stimulation (TSH-Tg) are highly likely to harbor residual tumor. TSH stimulation can be achieved using either thyroid hormone withdrawal or recombinant human TSH (rhTSH). Highly skilled screening neck ultrasonography can identify a few additional patients with subcentimeter residual neck lymph node metastases not detected by TSH-Tg. However, ultrasonography and chest computed tomography (CT) are most critical for tumor localization in those patients with Tg values that suggest residual disease or in those patients with persistent antithyroglobulin antibodies (TgAb) that falsely lower Tg measurement. TgAb quantitative titers typically resolve steadily over just a few years in patients free of disease after initial therapy. Another paradigm shift is the recognition that most patients who eventually achieve freedom from disease do so by surgery with fewer patients cured by repetitive radioiodine treatments, and even fewer cured with external beam radiation. Patients who appear to be free of disease require a lifetime of follow-up to optimize levothyroxine treatment, and they will undergo periodic stimulation testing because some will still manifest recurrent disease. Patients with persistent disease despite negative ultrasonography, chest CT, and whole-body radioiodine imaging may have a tumor identified by fluorodeoxyglucose positron emission tomography, optimally performed with combined TSH stimulation and image fusion with CT or magnetic resonance imaging. Patients with metastatic disease who are unresponsive to conventional treatment are encouraged to participate in increasingly available thyroid cancer-specific clinical trials using targeted experimental oral or intravenous chemotherapeutic agents to address this tumor that has historically proven resistant to conventional chemotherapeutic agents.

Antineoplastic Agents↗
PubMed1999

Loss of heterozygosity of the long arm of chromosome 7 in follicular and anaplastic thyroid cancer, but not in papillary thyroid cancer.

Papillary thyroid cancer (PTC), but neither the follicular nor the anaplastic histotype [follicular thyroid cancer (FTC), anaplastic thyroid cancer (ATC)], overexpresses simultaneously the protooncogene HGF (hepatocyte growth factor) and its receptor HGF-R (or c-met). Because 1) HGF and c-met map to chromosome 7q21 and 7q31, respectively, 2) FTC loses genetic material at multiple loci with a frequency much higher than PTC, and 3) loss of heterozygosity (LOH) on 7q has been previously found in various tumors, we tested the hypothesis that both FTC and ATC, but not PTC, could harbor LOH in segments of 7q encompassing the loci for HGF and c-met. We screened 6 normal thyroids, 10 colloid nodules, 10 follicular hyperplasias, 10 oncocytic adenomas, 10 follicular adenomas (FA), 10 FTC, 6 ATC, 12 PTC using two microsatellite markers for HGF, and two for c-met. LOH for all 4 markers was found in 100% of FTC, 100% of ATC, and (for only 1 or 2 markers) in 10-29% of FA. This is the first demonstration of an LOH that separates both FTC and ATC from PTC, in the best possible manner: 100% vs. 0%. Clearly, each of the two segments we have probed contains at least one tumor suppressor gene, whose inactivation is crucial for the establishment of the FTC (and ATC) phenotype. This loss of genetic material explains why FTC and ATC, but not PTC, fail to express both HGF and c-met. Our findings may also have immediate diagnostic application, in the context of assisting pathologists in the often difficult task of distinguishing FA from FTC.

Adenocarcinoma, Follicular↗
PubMed1997

Cytologic morphometric approach for the prediction of lymph node involvement in papillary thyroid cancer.

OBJECTIVE: Papillary thyroid cancer frequently metastasizes to lymph nodes; however, it is generally difficult to make a precise diagnosis preoperatively. The present study was carried out to evaluate lymph node status preoperatively by using quantitative estimations of various cytologic features obtained by fine needle aspiration biopsy from 110 patients with papillary thyroid cancer. STUDY DESIGN: Using a microscope connected to a computerized video system, mean nuclear area (NA) mean circumferential length of nuclei (CL), circular rate (CR), largest to smallest diameter ratio of nuclei (LS), coefficient of variation of NA (NACV), and rates of intranuclear cytoplasmic inclusions (CIs) and nuclear grooves (NG) were calculated and analyzed. RESULTS: LS, NACV and NG were significantly higher in cases with metastasized lymph nodes than node-negative cases (P < .05, P < .0001, P < .05, respectively). Furthermore, all parameters except CR and LS correlated exactly with the histopathologic features (P < .0001). The number of positive lymph nodes correlated well with the value of NACV, and all cases with recurrences proved to have NACV > 22%. CONCLUSION: Preoperative quantitative estimations of cytologic features are useful parameters for the prediction of lymph node metastases in papillary thyroid cancers.

Adolescent↗
PubMed1991

[Prognostically relevant factors in papillary thyroid cancer].

Papillary cancer have the best prognosis of all thyroid carcinomas with a five year survival rate of 98%. Between 1.1.1964 and 31.12.1987 we have operated 86 patients due to an papillary thyroid carcinoma. The five year respectively ten year survival rate was 88% respectively 75%. Prognostic relevant factors were as follows: metastasis, tumor stage, tumor invasion of vessels, multifocal tumor growth, age, pT differentiation and the tumor size.

Adenocarcinoma↗
PubMed2006

VEGF-C and COX-2 expression in papillary thyroid cancer.

In papillary thyroid cancer (PTC), age appears to be the most important single prognostic factor. Another characteristic feature is the lack of association between survival and lymph node metastases. Earlier, we found that expression of cyclooxygenase-2 (COX-2) is higher in older PTC patients, in agreement with the finding that older patients have a worse prognosis. Recent findings suggest that COX-2 can up-regulate vascular endothelial growth factor-C (VEGF-C) expression. Here, we investigated whether expression of VEGF-C differs between young and older PTC patients and whether expression of VEGF-C and COX-2 are correlated. Our retrospective study comprised 106 PTC patients selected by age: those under 35 or over 55 at diagnosis. Paraffin-embedded tissue samples were analysed by immunohistochemistry for VEGF-C protein expression. Furthermore, we investigated by quantitative RT-PCR and enzyme immunoassay the relationship between VEGF-C and COX-2 expression in papillary thyroid cancer cells (NPA cells). VEGF-C expression was significantly increased with age. In the tumours from older lymph node-positive (N1) patients, VEGF-C expression was significantly higher than in the tumours from young N1 patients. Moreover, all patients who died of cancer or who developed distant metastases were old, and most tumours from these patients (4 of 5) expressed VEGF-C and had had nodal metastases at the time of primary operation. Immunohistochemically, expression of COX-2 and VEGF-C correlated strongly. In cell culture, this correlation was not so clear, because the COX-2 selective inhibitor, NS-398, did not reduce VEGF-C expression. However, as both COX-2 and VEGF-C were induced by the tumour promoter phorbol 12-myristate 13-acetate (PMA), the same factors may control them both.

Adult↗
PubMed1998

Tall cell variant of papillary thyroid cancer.

Papillary histologic type is the most common form of thyroid carcinoma amounting to 85% cases. This pathology presents a rather good prognosis, but a few years ago, new subtypes have been described. Some of these variants show a fairly good prognosis i.e follicular, macropapillary, encapsulated while others appear to have a decidedly worse one, columnar cells, diffused sclerosing, or even to be clearly malignant as in the case of the tall cell variant. The authors report a case treated by a combined surgical and radiometabolic therapy and evidence the main characteristics of this rare and underestimated neoplasia.

Carcinoma, Papillary↗
PubMed2026

Myeloid landscape of BRAF-mutant papillary thyroid cancer and thyroiditis.

Papillary thyroid cancer (PTC) is less aggressive when associated with lymphocytic thyroiditis (LT), even in the presence of oncogenic BRAF, including smaller tumours, less lymph node involvement and reduced extrathyroidal extension. To investigate possible immune mechanisms underlying this association, we compared the tumour microenvironment of PTC-BRAF with LT and that without LT using single-cell RNA sequencing (scRNA-seq). Single-cell libraries were generated from fresh and fixed tumour samples with post-dissociation viability >70% using the 10x Genomics Chromium Platform and sequenced on an Illumina NovaSeq 6000. We analysed scRNA-seq data from 11 PTC-BRAF tumours: four with LT (one publicly available sample) and seven without LT. Downstream analyses included quality control, batch correction, dimensionality reduction, and differential gene expression analysis. We found that neutrophils were the predominant myeloid cell type in PTCs without LT. Thyrocytes without LT showed significant expression of the neutrophil recruitment chemokine ECRG4. In the absence of LT, neutrophils expressed oncogenic genes with poor clinical outcomes. In contrast, thyrocytes from tumours with LT showed increased expression of MHC-II antigen presentation, consistent with effective immune surveillance. Thyrocytes and macrophages in the presence of LT showed enrichment of interferon gamma response pathways. Our data suggest that LT in thyroid cancer is associated with enhanced antigen presentation and fewer features of pro-tumourigenic innate immune activity. These results identify previously under-recognised innate immune cell population and associated transcriptomic features, which suggest new mechanisms to target immune treatments in PTC refractory to other therapies.

Humans↗
PubMed1998

[Microscopic thyroid papillary cancers presenting as cervical lymph node metastases].

Microscopic papillary thyroid cancer (< 1 cm in diameter) is reputed to have an excellent prognosis. In 10 to 20% of cases, it presents in the form of lymph ode metastases. Immediately metastatic forms can be associated with unfavourable prognostic factors, such as multifocal tumours, extension to adjacent tissues, capsular effraction and development of distant metastases. We report 4 cases of microscopic papillary thyroid cancer presenting in the form of lymph node metastases. No primary thyroid lesion was palpable in any of these patients, but the subsequent course was complicated by ling metastases in one case. All patients underwent total thyroidectomy with lymph node dissection followed by adjuvant therapy with radioactive iodine and thyroxin inhibitory treatment. Lung metastases were observed in one case. The authors propose a therapeutic approach based on analysis of severity factors, which determine the recurrence rate.

Adult↗
PubMedDate not supplied

[Study of HRas1 minisatellite frequencies in children with thyroid papillary cancer].

The "rare" alleles of HRas1 gene minisatellite are well-known factor of predisposition to many kinds of cancer. We have studied HRas1 minisatellite frequencies among patients with papillary thyroid cancer which is related to consequences of Chernobyl accident. The HRas1 minisatellite was analysed in 32 patients who suffered from papillary carcinoma and underwent operation in 1996-2001 and in 75 Belorussian residents. Of 64 HRas1 alleles revealed in patients 14 were defined as "rare" (21.9%); in the control group we have detected 17 "rare" alleles (11.3%) of the examined 150 alleles. The higher frequency of "rare" HRas1 minisatellite alleles in patient group was statistically significant (p < 0.01). We can suppose that the "rare" alleles of HRas1 minisatellite are associated with increased risk of papillary thyroid cancer formation in children and adolescents after Chernobyl accident.

Adenocarcinoma, Papillary↗