Showing papers on "Papillary thyroid cancer published in 2003"

BRAF Mutation in Papillary Thyroid Carcinoma

Abstract: The BRAF gene has been found to be activated by mutation in human cancers, predominantly in malignant melanoma. We tested 476 primary tumors, including 214 lung, 126 head and neck, 54 thyroid, 27 bladder, 38 cervical, and 17 prostate cancers, for the BRAF T1796A mutation by polymerase chain reaction (PCR)-restriction enzyme analysis of BRAF exon 15. In 24 (69%) of the 35 papillary thyroid carcinomas examined, we found a missense thymine (T)-->adenine (A) transversion at nucleotide 1796 in the BRAF gene (T1796A). The T1796A mutation was detected in four lung cancers and in six head and neck cancers but not in bladder, cervical, or prostate cancers. Our data suggest that activating BRAF mutations may be an important event in the development of papillary thyroid cancer.

Clinical Implication of Hot Spot BRAF Mutation, V599E, in Papillary Thyroid Cancers

Abstract: Activating mutations in the BRAF kinase gene have recently been reported in human cancers. The aim of the present study was to determine the frequency of BRAF mutations in thyroid cancer and their correlation with clinicopathological parameters. We analyzed exons 11 and 15 of BRAF gene in six human thyroid cancer cell lines and 207 paraffin-embedded thyroid tumor tissues. A missense mutation was found at T1796A (V599E) in exon 15 in four of the six cell lines and 51 of 207 thyroid tumors (24.6%; 0 of 20 follicular adenoma, 0 of 11 follicular carcinoma, 49 of 170 papillary carcinomas, and 2 of 6 undifferentiated carcinomas). Activation of MAPK kinase-MAPK pathway was observed in cell lines harboring BRAF mutation. BRAF mutation-associated enhanced cell growth was suppressed by MAPK kinase inhibitor, U0126. Examination of 126 patients with papillary thyroid cancer showed that BRAF mutation correlated significantly with distant metastasis (P = 0.033) and clinical stage (P = 0.049). Our results indicate that ...

Prevalence and risk of cancer of focal thyroid incidentaloma identified by 18F-fluorodeoxyglucose positron emission tomography for metastasis evaluation and cancer screening in healthy subjects.

Abstract: We performed a retrospective review of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) examination to determine the prevalence of thyroid FDG-PET incidentaloma in a patient group evaluated for metastasis of cancer and in a group of healthy subjects who underwent voluntary cancer screening. We also evaluated the risk of malignancy in focal thyroid FDG-PET incidentaloma and its association with standard uptake values (SUVs) (maximum and greater than 0.75 threshold). A total of 1330 subjects underwent FDG-PET for metastasis evaluation (n = 999) and cancer screening (n = 331). Twenty-nine of 1330 subjects (2.2%) showed focal (n = 21) or diffuse (n = 8) thyroid FDG-PET incidentaloma. There was no significant difference in the prevalence of thyroid FDG-PET incidentaloma between the two groups (19 of 999 vs. 10 of 331; P > 0.05). Four of 15 focal incidentalomas (26.7%) whose histological diagnoses were available showed papillary thyroid cancer. The maximum SUV (16.5 +/- 4.70) and greater than 0.75 threshold SUV (14.2 +/- 5.3) of malignant lesions were significantly higher than those of benign tumors (6.5 +/- 3.8 and 4.9 +/- 3.0; P < 0.05). In conclusion, thyroid FDG-PET incidentaloma has prevalence of 2.2%, and its prevalence was not different according to the purpose of the FDG-PET. The focal thyroid FDG-PET incidentaloma carries a high risk of malignancy, especially in cases with high SUVs. Therefore, focal thyroid FDG-PET incidentaloma with high SUVs warrants a pathological diagnostic procedure if it changes a patient's treatment plan or prognosis.

Methylation of the Thyroid-stimulating Hormone Receptor Gene in Epithelial Thyroid Tumors: A Marker of Malignancy and a Cause of Gene Silencing

Abstract: Thyroid-stimulating hormone receptor (TSHR) expression is frequently silenced in epithelial thyroid cancers associated with decreased or absent TSH-promoted iodine uptake. To study the underlying molecular mechanism of decreased TSHR expression, we examined the methylation status of the TSHR gene promoter by sequencing bisulfite-treated DNA from thyroid tumors. After identification of methylated sites by sequencing bisulfite-treated DNA, we used methylation-specific polymerase chain reaction and found frequent CpG methylation in papillary thyroid cancer (23 of 39 patients; 59%) and follicular thyroid cancers (7 of 15 patients; 47%). In contrast, we saw no methylation in normal thyroid tissues and benign adenomas (0 of 8 patients; 0%). In human thyroid tumor cell lines, we observed that TSHR was normally expressed at the protein and mRNA level in cells where the TSHR gene was unmethylated, whereas it was silenced in cell lines where the TSHR promoter was hypermethylated. Treatment of the latter cells with a demethylating agent partially restored TSHR expression. We thus demonstrate aberrant methylation of human TSHR as a likely molecular pathway responsible for the silencing of this gene in thyroid cancers. We propose that methylation of TSHR may provide a novel diagnostic marker of malignancy and a basis for potential use of demethylating agents in conjunction with TSH-promoted radioiodine therapy for epithelial thyroid cancers.

Diagnostic utility of thyroglobulin detection in fine-needle aspiration of cervical cystic metastatic lymph nodes from papillary thyroid cancer with negative cytology.

Abstract: Cystic changes in metastatic cervical lymph nodes (CLN) from papillary thyroid cancer (PTC) may be a diagnostic pitfall in fine-needle aspiration biopsy (FNAB) cytology. We investigated in a series of CLN metastases from thyroid cancers (TC), including cystic PTC, and from a wide spectrum of extrathyroidal malignancies, the diagnostic role for metastatic TC of the rapid detection of thyroglobulin in eluates from FNAB (FNAB-Tg) of CLN. The study was carried out in a group of 79 subjects (22/57 M/F; median age, 56 years; range, 20-86 years) with enlarged CLN and thyroid nodules (TN), examined for potential metastatic TC, and harboring a large spectrum of incidentally diagnosed extrathyroidal malignancies (n = 24, mostly represented by lymphomas, lung, and breast cancers), CLN metastases from thyroid cancers (n = 28, including 6 cystic metastatic PTC), 6 specific lymphadenitis and 21 reactive lymphadenitis mostly detected (n = 16) during follow-up of patients with previously ablated TC. Markedly high FNAB thyroglobulin (Tg) values were found in all metastatic CLN TC. Two of the six cases with cystic metastatic CLN PTC were diagnosed by FNAB-Tg but not by cytology. In conclusion, FNAB-Tg has been confirmed as an easy modality and fast procedure to diagnose CLN metastasis from TC and high FNAB-Tg values with nondiagnostic cystic cytology strongly suggest cystic metastatic PTC.

Diagnostic changes as a reason for the increase in papillary thyroid cancer incidence in Geneva, Switzerland

Abstract: Objective: Several studies have reported upward incidence trends of papillary thyroid cancer. It is unclear whether these trends reflect a real risk increase, by some attributed to iodine supplementation, or an artificial one, due to increased diagnostic activity or changed histological criteria. This study examines if these artificial factors explain the increased papillary thyroid cancer incidence in the Swiss canton of Geneva. Methods: All thyroid carcinomas (n = 436) recorded between 1970 and 1998 at the Geneva Cancer Registry were considered. European age-adjusted incidence trends were estimated using linear regression analysis. For papillary cancers we evaluated diagnostic modalities and way of presentation (in particular microcarcinoma < 1 cm or silent carcinoma). In addition, we reviewed the histological slides of follicular carcinomas. Results: Papillary thyroid cancer incidence increased significantly from 0.7 to 1.8/100,000 for men and from 3.1 to 4.3/100,000 for women between 1970–74 and 1995–98. The proportion of microcarcinomas and silent carcinomas increased from 17% to 24% between 1970–79 and 1990–98. At histological review, follicular cancers were more often reclassified as papillary cancer for cases diagnosed between 1970 and 1979 than for cases diagnosed between 1990 and 1998 (45% vs 25%, p = n.s.). Conclusions: The increasing papillary thyroid cancer incidence seems mainly due to changes in histological diagnostic criteria and, to a lesser extent, to increased diagnostic activity. If confirmed, the results of this study indicate that fears of increasing incidence rates of papillary thyroid cancer should not prevent implementation of adequate programs of iodine supplementation in the many areas where iodine deficiency still prevails.

Thyroid Carcinoma in the McCune-Albright Syndrome: Contributory Role of Activating Gsα Mutations

Abstract: McCune-Albright syndrome (MAS) is defined by the triad of cafe ´ -au-lait skin pigmentation, polyostotic fibrous dysplasia, and hyperfunctioning endocrinopathies, such as precocious puberty, hyperthyroidism, GH excess, and Cushing’s syndrome. This disorder is caused by sporadic, postzygotic activating mutations in the GNAS1 gene, which codes for the Gs protein in the cAMP signaling cascade. Nodular and diffuse goiters (with and without hyperthyroidism), as well as benign thyroid nodules, have been reported in association with MAS. Herein we report two cases of thyroid carcinoma in patients with MAS. The first is a case of papillary thyroid cancer detected incidentally during a hemithyroidectomy for hyperthyroidism in a 14-yr-old girl. The second is one of a 41-yr-old woman with long-standing MAS and an enlarging thyroid nodule, which was diagnosed as a clear cell thyroid carcinoma, a rare variant of thyroid cancer. Molecular analysis revealed that foci of malignancy and adjacent areas of hyperplasia and some areas of normal thyroid harbored activating mutations of Arg 201 in the GNAS1 gene. These findings suggest that the infrequent development of thyroid carcinoma in MAS patients involves additional mutational or epigenetic events. (J Clin Endocrinol Metab 88: 4413– 4417, 2003)

Hypermethylation, but not LOH, is associated with the low expression of MT1G and CRABP1 in papillary thyroid carcinoma.

Abstract: We previously obtained gene expression profiles of 8 matched papillary thyroid carcinoma (PTC) and normal tissues using DNA microarrays. To identify novel tumor suppressor genes involved in thyroid carcinogenesis, we here analyze genes showing lower expression in PTC tumors than in normal thyroid tissues. A search for loss of heterozygosity (LOH) in 49 regions that harbor consistently down-regulated genes revealed LOH in only 4 regions and in just a very small number of tumors. To determine whether the underexpression might be due to promoter methylation, we used combined bisulfite restriction analysis and bisulfite sequencing to study 7 underexpressed genes. Loss of expression of MT1G and CRABP1 is accompanied by hypermethylation in the 5' regions of these genes, but methylation was not seen in other genes tested. Combined treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-Aza-dC) and the histone deacetylase inhibitor trichostatin A (TSA) resulted in demethylation and re-expression of the MT1G gene in the cell line K2. Treatment with 5-Aza-dC alone restored CRABP1 expression in a colorectal cancer cell line, SW48. In conclusion, LOH is a remarkably rare mechanism of loss of gene function in PTC. In contrast, hypermethylation of promoter CpG islands seems to occur at higher frequency. MT1G and CRABP1 are novel genes that are likely involved in the pathogenesis of sporadic PTC.

The selective tyrosine kinase inhibitor, STI571, inhibits growth of anaplastic thyroid cancer cells.

Abstract: To establish a molecular targeting therapy for anaplastic thyroid carcinomas, we studied the effect of the specific tyrosine kinase inhibitor, STI571, on anaplastic thyroid cancer cell lines highly expressing c-ABL ARO (mutated p53) and FRO (undetectable p53) These lines showed marked inhibition of cell growth after treatment with STI571 In contrast, the growth of papillary thyroid cancer cell lines that harbor wild-type p53 and have low levels of c-ABL was not affected by STI571 Fluorescent-activated cell sorting analysis revealed that STI571 treatment increased the fraction of FRO and ARO cells in S and G(2)/M phases, respectively, indicating induction of S and G(2)/M transition arrest These changes were accompanied by inhibition of c-ABL phosphorylation/activation and increased expression of p21(cip1) in FRO and p27(kip1) in both FRO and ARO cells Treatment with STI571 also led to reduction of cyclin A, B1, and CDC2 levels The growth of FRO cells implanted into immunocompromised mice was significantly inhibited by STI571 Taken together, these results suggest that selective suppression of c-ABL activity by STI571 may represent a potential anticancer strategy for p53-mutated undifferentiated thyroid carcinomas

Familial risk of cancer by site and histopathology.

Abstract: Familial risks for histopathology-specific cancers have not been determined. We used the nationwide Swedish Family-Cancer Database on 10.2 million individuals and 1 million tumors to calculate standardized incidence ratios (SIRs) for familial cancers of specific histology and morphology among 0- to 66-year-old offspring. We used histology codes for both offspring and parents, but because of the limited number of cases, the morphology-specific classification could be used only for offspring by all site-specific cancers in parents, resulting in inflated risk estimates. A number of novel findings emerged in the histopathology-specific analysis of familial risks, in addition to some known associations. Overall, specific histology showed an SIR of 2.07 for all cancers compared to an SIR of 2.00 for any histology. However, the small effect was due to breast and prostate cancers, which showed a negligible effect of specific histology. Familial risks of over 4.0 were found for serous papillary cystadenocarcinoma of the ovary, papillary thyroid cancer and low-grade astrocytoma. Familial risks of over 3.0 were found for signet-ring gastric cancer, various forms of ovarian cancer and squamous cell skin cancer. Also noteworthy were familial risks of hepatocellular carcinoma (2.48), pancreatic adenocarcinoma (1.92), large cell carcinoma and adenocarcinoma of the lung (2.29 and 2.18, respectively) and clear cell carcinoma of the kidney (2.73). Many of the findings were novel and could be revealed only by applying codes for specific histopathology. These data call for a closer description of familial aggregations and probing for the underlying genetic mechanisms.

Increased expression of phosphorylated p70S6 kinase and Akt in papillary thyroid cancer tissues.

Abstract: Although a number of abnormalities in oncogenes have been reported in thyroid neoplasms, little information is available on the signal transduction pathway involved in neoplastic thyroid cell growth. Both p70S6 kinase (p70S6K) and Akt are kinases downstream of phosphatidylinositol 3 kinase (PI3K). These kinases are phosphorylated and activated by growth factors including IGF-1, EGF/TGF-alpha, and HGF in thyroid cells. Since the receptors for these growth factors are reportedly overexpressed in human thyroid cancer, we hypothesized that the PI3K-mediated signalings are overactivated in thyroid cancers. Tumorous and adjacent normal tissues of 20 patients with papillary thyroid cancer were obtained at surgery, and expression of p70S6K and Akt were measured by Western blot. Expression of the protein levels of p70S6K was increased in tumor tissues (T) compared to normal thyroid tissues (N), and expression of phosphorylated p70S6K was also significantly increased in tumor than in surrounding normal tissues. Overexpression of p70S6K in tumor tissues was further confirmed by immunohistochemistry. Strong immunoreactivity in the cytoplasm of thyroid cancer cells was seen in the majority of cases, whereas little immunoreactivity was found in the surrounding normal portion. Expression of phosphorylated Akt (pAkt) was also significantly higher in tumor tissues. Phosphorylation of Bad (pBad), a substrate of Akt, was also increased in the tumor tissues in association with activation of Akt, and the T/N ratio for pAkt positively correlated to the T/N ratio for pBad. The data presented here demonstrate that both p70S6K and Akt are activated in the majority of human papillary cancer cells. Activation of these signalings may be involved in the progression of papillary carcinoma by stimulating cell proliferation and/or preventing apoptosis.

Value of external irradiation for locally advanced papillary thyroid cancer.

Abstract: Purpose: To look for the possible efficacy of external beam irradiation (EBRT) for locally advanced papillary thyroid cancers Methods and materials: Between August 1981 and September 1997, 91 patients with locally advanced papillary thyroid cancers (pathologic Stage T4 or N1) were treated with surgical resection. After surgery, 23 patients received postoperative EBRT with or without ablative radioiodine therapy, and 68 patients were treated with ablative radioiodine therapy alone. The distribution of age, gender, and stage was comparable in both groups. Results: The overall survival rates at 7 years were not significantly different statistically between the two groups at 98.1% for the no-EBRT group and 90% for the EBRT group (p = 0.506). The locoregional control rates at 5 years were significantly different (EBRT 95.2% and no EBRT 67.5%; p = 0.0408). Analysis of the prognostic factors, age, gender, stage, and use of radioiodine ablative therapy, indicated these were not significant variables, except for EBRT. Conclusion: Adjuvant postoperative EBRT did not affect overall survival, but significantly improved locoregional control in patients with locally advanced papillary thyroid cancer (Stage pT4 or lymph node involvement).

Anaplastic thyroid cancer evolved from papillary carcinoma: demonstration of anaplastic transformation by means of the inter-simple sequence repeat polymerase chain reaction.

Abstract: Background In thyroid tumors, the coexistence of well- and poorly differentiated tumor types has led to the hypothesis that poorly differentiated thyroid tumors develop from well-differentiated thyroid tumors. By evaluating the genomic instability of histologically distinct but coexisting tumor foci, this study aimed to develop an improved understanding of thyroid tumorigenesis and tumor evolution. Design Laser capture microdissection (LCM) was carried out on archival formalin-fixed, paraffin-embedded sections from a tumor containing foci of classic papillary thyroid cancer and anaplastic thyroid cancer. DNA was extracted from each microdissected tumor focus. In addition, cryopreserved bulk normal and neoplastic thyroid tissue underwent DNA extraction. All DNA samples were subsequently evaluated for genomic instability by means of inter–simple sequence repeat polymerase chain reaction. Results The LCM DNA from each archival paraffin-embedded tumor focus demonstrated unique patterns of banding as compared with the cryopreserved tumor and normal tissue DNA. Thus, intratumoral variability in genomic instability was observed. Comparison of inter–simple sequence repeat polymerase chain reaction patterns of LCM DNA from adjacent foci of papillary and anaplastic tumors showed conserved genome alterations. Conclusions At the genome level, thyroid tumors may be highly heterogeneous. The intratumoral histologic heterogeneity observed in thyroid neoplasms reflects genetically heterogeneous underlying tumor cell populations that are demonstrated by the observed differences in their rates and extents of genomic instability. The conserved genomic alterations in the microdissected papillary and anaplastic foci suggest intratumoral evolution, with transformation of a preexisting papillary tumor to anaplastic carcinoma.

Sentinel lymph node biopsy in thyroid tumors: a pilot study

Abstract: The purpose of this study was to assess the feasibility of sentinel lymph node (SLN) biopsy in thyroid neoplasms. Ten patients with uninodular thyroid disease and no evidence of lymph node metastases were examined. Lymph node mapping was performed by preoperative lymphoscintigraphy and intraoperative use of a hand-held gammaprobe. Following thyroidectomy, the SLN(s) were selectively excised and worked-up histologically for occult metastases. Overall detection of SLNs was possible in 50% of the cases with lymphoscintigraphy and in 100% with the gammaprobe. All SLNs in the lateral compartment and upper mediastinum were accurately detected with lymphoscintigraphy. One patient with a papillary carcinoma showed a metastasis in the SLN. One patient experienced temporary lesion of the recurrent laryngeal nerve. In conclusion, sentinel lymph node biopsy is technically feasible. The combination of lymphoscintigraphy and gammaprobe accurately reveals SLNs in the central and lateral compartment and in the mediastinum. Search for SLNs in the lower central compartment enhances the risk of injuring the recurrent laryngeal nerve. The clinical relevance of SLN biopsy in papillary thyroid cancer is unclear, and the subgroup of patients benefiting from it has still to be defined.

Evaluation of the levels of bFGF, VEGF, sICAM-1, and sVCAM-1 in serum of patients with thyroid cancer.

Abstract: Tumour growth and development depend on a complex cascade of angiogenic factors. The aim of the study is evaluation of the level of growth factors VEGF and bFGF, and adhesion molecules sICAM-1, s VCAM-1 in the serum of patients with papillary thyroid cancer. The study comprised 35 patients aged 21–68 years (mean age 46±14) who had papillary thyroid cancer diagnosed on the basis of thin needle aspiration biopsy, and were qualified for operative treatment. This group comprised 28 women and seven men. The control group was 26 healthy individuals. Serum concentrations of bFGF, VEGF, slCAM-1, and sVCAM-1 were evaluated by the enzyme-linked immunosorbent assay (ELISA) method. We have observed significantly higher mean concentrations of bFGF, VEGF, and sICAM-1 in the serum of patients with thyroid cancer compared with the control group. There was no significant difference between the sVCAM-1 concentrations of the thyroid cancer group and the control group.

Preoperative plasma concentrations of vascular endothelial growth factor and matrix metalloproteinase 9 are associated with stage progression in papillary thyroid cancer

Abstract: OBJECTIVE Vascular endothelial growth factor (VEGF), a potent angiogenic peptide, and matrix metalloproteinase 9 (MMP-9), a proteolytic enzyme, are found to be abundantly expressed in several types of cancer and correlate with tumour progression. In this study, we investigated the relationship between preoperative plasma VEGF, MMP-9 levels and disease stages in papillary thyroid cancer. DESIGN Plasma samples were consecutively collected from 30 patients with papillary thyroid cancer preoperatively (seven males and 23 females with a mean age of 45 +/- 16 years) and control plasmas obtained from 30 patients with benign goitre (seven males and 23 females with a mean age of 44 +/- 18 years) and 23 healthy persons (four males and 19 females with a mean age 44 +/- 15 years). Plasma VEGF and MMP-9 concentrations were determined by enzyme-linked immunosorbent assay. Cancer progression was staged by the TNM classification of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC). RESULTS In thyroid cancer patients, the plasma VEGF and MMP-9 values were higher than those in controls (51.8 +/- 11.5 ng/l vs. 27.0 +/- 0.8 ng/l; 72.3 +/- 23.3 micro g/l vs. 22.1 +/- 3.0 micro g/l, respectively; P < 0.05), and those in benign goitre (51.8 +/- 11.5 ng/l vs. 39.7 +/- 8.8 ng/l; 72.3 +/- 23.3 micro g/l vs. 23.0 +/- 2.2 micro g/l, respectively; P < 0.05). But, there was no difference of plasma VEGF and MMP-9 between patients with goitre and normal subjects. A comparison of VEGF and MMP-9 levels in patients at each cancer stage and in patients with benign nodule found that plasma VEGF and MMP-9 values in TNM stages III and IV, but not stage I or II, were significantly elevated (P < 0.05). When cancer patients were grouped according to clinopathological features, the plasma VEGF and MMP-9 concentrations were both significantly elevated in patients with large tumour size (P < 0.01), lymph node involvement (P < 0.01), extrathyroidal invasion (P < 0.05), distant metastasis (P < 0.05) or advanced stages (P < 0.01). CONCLUSION Our study demonstrated that circulating VEGF and MMP-9 levels correlated with progression of papillary thyroid cancer, suggesting plasma VEGF and MMP-9 may serve as preoperative adjuvant markers for assessing disease activity in papillary thyroid cancer. However, they should not be used as a diagnostic tool for differentiating malignant from benign thyroid disorders.

Papillary carcinoma of the thyroid gland

Abstract: Papillary thyroid cancer is after ovarian cancer the most frequent malignant disease of the endocrine system and because of this fact, early detection and appropriate surgical treatment is essential. Radical surgical treatment lower the risk of the disease relapse and postoperative adjuvant therapy with radioiodine is possible as well as postoperative follow up with thyreoglobulin measurement. If the total thyroidectomy is performed in highly specialized institution the risk of postoperative complications is acceptable and therefore is the treatment of choice for papillary thyroid cancer. Only the patients with occult papillary thyroid cancer can be treated with hemithyroidectomy. In our series of 410 patients the majority of the patients (85.12%) were in the early phase of the disease and the degree of successfully performed radical surgery for papillary thyroid cancer was very high (tumor reduction was performed in only 1.46% of cases).

Risk of thyroid cancer and high prevalence of hepatitis C virus

Abstract: Some studies report an increased risk of autoimmune thyroid disease in hepatitis C and B as well as in interferon therapy. Recently a new link between HCV and papillary thyroid cancer has been published. The mechanism responsible for the oncogenetic role of HCV is not well understood, but it involves immunity system and autoimmunity disorders. We designed a case-control study on HCV exposure. To assess the positivity to HCV ELISA test and polymerize chain reaction technique (PCR) were used. For statistical analysis an odds ratio and corresponding 95% confidence intervals were computed using unconditional multiple-logistic-regression models. Our findings show a statistically significant association between HCV and papillary thyroid cancer (OR = 3.3, 95% CI 1.5-7.4, p=0.003), overall in female gender (OR = 3.3, 95% CI 1.2-8.7, p=0.01) and in the > or =50 years age category the risk for thyroid cancer was confirmed by the OR = 3.2 (95% CI 1.3-7.9, p=0.01). Based on our study there is an association between HCV and thyroid cancer and it is more readily detectable in countries with a high prevalence of HCV.

Influence of iodine deficiency and iodine prophylaxis on thyroid cancer histotypes and incidence in endemic goiter area.

Abstract: The aim of the study was to evaluate the correlation between thyroid cancer histotype and incidence rate (IR) and iodine nutrition level in two endemic goiter areas: the districts of Krakow and Nowy Sacz. The suspension of iodine prophylaxis in Poland in 1980 resulted in increased goiter prevalence in schoolchildren and adults and elevated TSH levels in newborns in the early 1990s. Since 1992 a rise in thyroid cancer IR was observed. Thyroid cancer IR in the Krakow population was 2.22 in 1986; 3.62 in 1995 and 6.02 in 2001; in Nowy Sacz: 1.52; 2.59 and 3.88 respectively. In 1986 papillary/follicular cancer ratio in both areas was about 1.0--the value typical of iodine deficient areas. After restoring the obligatory iodine prophylaxis in 1997, a significant decrease in elevated TSH concentration in newborns and urinary iodine concentration increase in schoolchildren were observed. A relative rise in the incidence of papillary thyroid cancer and decrease in follicular cancer, resulting in rise in papillary/follicular thyroid cancer ratio up to 5.9 in 2001 was also observed. Since 1999 no further thyroid cancer IR increase was noted. In conclusion, a significant increase in differentiated thyroid cancer IR was observed in association with the iodine prophylaxis suspension. Changes in thyroid cancer histotypes in 1986-2001 and a significant decrease in incremental rate of differentiated thyroid cancer probably reflect the influence of effective iodine prophylaxis. The significant difference between IR of thyroid cancer incidence in the districts of Krakow and Nowy Sacz may be related to differences in the exposure to radiation after the Chernobyl accident.

Follicular carcinoma of the thyroid gland

Abstract: Follicular thyroid cancer is the second most common thyroid malignancy. This tumor has a predisposition for hematogenous dissemination an extra thyroid spread. Accurate cytological diagnosis of follicular thyroid cancer is not possible and this fact highlights the necessity for surgical treatment of any suspicious thyroid nodule. Aggressiveness of this tumor is greater than in the case of papillary thyroid cancer and it is the reason for radical surgical treatment of follicular thyroid cancer. Total thyroidectomy facilitates later adjuvant therapy with thyroid hormones and radioiodine. This procedure improves the outcome and the risk of relapse. Results of our study clearly demonstrate that diagnosis of follicular thyroid cancer in us is established in the early phase of the disease (78.57%), but the significant number of the patients (21.43%) is still in the advanced phase of the disease.

Iodine-131 uptake in focal bronchiectasis mimicking metastatic thyroid cancer.

Abstract: A 54-year-old woman underwent total thyroidectomy for papillary thyroid cancer and ablation therapy with a 7.4-GBq (200-mCi) therapeutic dose of 1-131 7 months earlier. This was followed by repeated 1-131 scintigraphy. An area of focal 1-131 uptake persisted in the left lower lung. Her serum thyroglobulin level remained below detection limits. A computed tomographic scan of the chest showed focal bronchiectasis in the left lower lung, at the same site as the hot spot on the I-131 scintigram. Fiberoptic bronchoscopy revealed no endobronchial mass or mucosal destruction in the left lower lung.

Occult papillary thyroid carcinoma in postmortem species: prevalence at autopsy

Abstract: Objective: The purpose of this study was to determine the prevalence of occult papillary thyroid cancer (OPTC) in a sample of cadavers from Guatemala, a country in Central America Study design and setting: This was a cross-sectional study of cadaver samples We analyzed 150 glands that were removed during autopsy from 150 cadavers (34 women and 116 men) who were admitted to the morgue of the Judicial Bureau between January and March 2000 Results: A total of 17 glands showed macroscopic evidence of disease, but only 3 glands (1 female and 2 males) showed microscopic evidence of malignancy This corresponded to a 2% prevalence rate (range, 04–57%) The sex prevalence of OPTC was 29% (range, 007–15%) for females and 17% (range, 02–61%) for males No significant difference was noted (P = 47, exact unconditional test) The male-to-female ratio was 1:17 Conclusion: We concluded that the prevalence of OPTC in Guatemala is low but comparable to literature reports Occult papillary thyroid carcinoma appears to have no sex predilection as opposed to the clinically evident papillary thyroid carcinoma, which develops more commonly in females Significance: Occult papillary thyroid carcinoma is a much more common pathology than clinically evident thyroid cancer, and the clinical implications still need to be determined

Papillary thyroid cancer: high inter-(simple sequence repeat) genomic instability in a typically indolent cancer.

Abstract: Objectives. The object of this study is to measure genomic instability in papillary thyroid cancer and correlate these measurements with known clinical prognosticators such as patient age, tumor size, histologic subtype, and three commonly used thyroid risk assessment indices. A secondary objective of this study was to use the measurements of genomic instability to estimate the number of mutational events present in the papillary thyroid cancer genome. Methods. Inter-simple sequence repeat polymerase chain reaction (ISSR-PCR) is a rapid and reproducible technique for quantitation of genomic instability, or the degree of genome alteration, in solid tumors. This includes quantitation of amplifications, deletions, translocations, and insertions. Twenty-eight papillary carcinomas were evaluated by ISSR-PCR. Results. Evaluation of 28 papillary carcinomas by ISSR-PCR demonstrated a wide range of genomic instability. Of the panel of clinicopathologic factors examined, only patient age was significantly associated with genomic instability. The mean genomic instability index value was greatest in the youngest age group, which was significantly different from the median value measured in the oldest age group (3.7, 2.5, respectively, p = .05). The mean value in the intermediate age group fell between the younger and older groups (3.1). By use of ISSR-PCR, we have calculated 15,000 individual genomic events as having occurred in each papillary tumor cell. Conclusions. Despite its generally indolent biologic behavior, papillary thyroid cancer exhibits a high degree of genomic instability comparable to that seen in colorectal cancer. These results suggest that elevated genomic instability, as measured by ISSR-PCR, may not be sufficient to enable thyroid tumor progression to less indolent disease and that this process is severely constrained by some additional essential factor such as the differentiated state of the tissue or the need to bring into play an additional form of genomic destabilization. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 825–832, 2003

A report of six cases of familial papillary thyroid cancer.

Abstract: Aims: Familial occurrence of papillary thyroid cancer is uncommon. The purpose of this study was review our own experience in a series of 267 papillary thyroid cancers. Methods: We analysed the clinical records of 267 consecutive patients operated on for papillary thyroid cancer (PTC) in our hospital between June 1980–March 2000. Results: We identified a family history in three families (6 patients), which results in a 2.25% familial papillary thyroid carcinoma (FPTC) rate. Pathology findings revealed that the tumour was multifocal and bilateral in 2 patients. Lymph-node metastases were found in 4 patients. They are all alive with a mean time of follow-up of 74.3 months (range 2–120). Conclusions: We recommend that patients with familial disease should be treated according to the disease stage and other risk factors, similar to those with sporadic differentiated papillary thyroid cancer. We encourage the further reporting and pedigree analysis to identify patients affected by FPTC.

Protocol for the combined diagnostic and therapeutic use of recombinant human thyroid-stimulating hormone.

Abstract: Patients may be prepared for radioiodine diagnostic imaging by withdrawal of all thyroid medication or by the administration of extrinsic thyroid-stimulating hormone (TSH). Although purified human and bovine TSHs were used in the past, they are no longer recommended because of their adverse effects. Recently, a new extrinsic TSH called recombinant human TSH (rhTSH) was developed and is commercially available. It is a highly purified, recombinant form of the naturally occurring human TSH. It was introduced to decrease complications associated with temporary hypothyroid states required at times in the follow-up evaluation of patients with thyroid cancer. Although rhTSH is currently used for patient preparation in diagnosis only, its use in preparations for subsequent radioiodine therapy may be helpful in some clinical circumstances. The authors describe a patient with papillary thyroid cancer in whom a 2-day rhTSH protocol was used for diagnosis and extended for therapeutic purposes. The protocol was useful to obtain the diagnostic information needed to determine whether to treat, and it allowed rapid progress to therapy without further patient preparation. Until rhTSH is fully approved for both diagnostic and therapeutic uses, this modified 2-day protocol would allow patients with special clinical circumstances to be evaluated and treated rapidly.

Parapharyngeal lymph node involvement in papillary thyroid carcinoma.

Abstract: Papillary thyroid cancer extends to lymphatic nodes in approximately 40% of cases. Node involvement often occurs in the internal jugular and recurrent laryngeal chain on the side of the lesion. To the authors' knowledge, only 4 cases with 1-131 uptake in pharyngeal metastatic nodes have been reported previously in the literature. The authors report parapharyngeal node involvement demonstrated by 1-131 scintigraphy in a patient with papillary thyroid cancer.

Evaluation and Management of the Euthyroid Nodular and Diffuse Goiter

Abstract: Palpable thyroid nodules among adult individuals living in the United States are very common, with a prevalence of 4–7% (1). By contrast, the prevalence of nodules incidentally detected at autopsy, or by the use of high-resolution ultrasonography, has ranged from 20–65% in individuals without a prior history of thyroid disease (2–8). Thyroid nodules are more common in women, estimates varying from a female-to-male ratio of 1.2 : 1 (2,9) to 4.3 : 1 (10), and increase in prevalence with advancing age (11,12). The likelihood of a single palpable thyroid nodule being malignant is less than 10% and possibly closer to 5% (1,12,13). Nevertheless, because of the possibility of cancer, some clinicians, especially those in the surgical subspecialties, recommend that all nodules be removed. Other physicians, especially endocrinologists, recommend a more conservative approach in order to avoid unnecessary surgery. Thus, there is an ongoing debate regarding the appropriate evaluation and management of individuals with thyroid nodules. The main purpose of this chapter is to address these issues and to provide a clinically appropriate and cost-effective approach to the evaluation and management of nodular thyroid disease. There are also several excellent reviews, to which the reader is directed (1,11,14–17).

Thyroid Nodules and Thyroid Cancer

Abstract: Thyroid nodules are a common problem in clinical practice. The majority are benign lesions, predominantly follicular adenomas, although other common causes of benign lesions include cysts, multinodular goiters, colloid goiters, benign Hurthle cell neoplasms, and thyroiditis (1,2).However, some thyroid nodules may, in fact, represent thyroid cancer. The frequency of thyroid cancer in patients presenting with a solitary thyroid nodule has been estimated to be around 5% (2), but the overall prevalence of cancer in all patients with solitary nodules has been estimated to be 0.1–0.2% (3). Because thyroid nodules are so common, but, in general, only malignant nodules or benign ones large enough to cause compressive symptoms require operation, a cost-effective approach to the evaluation of thyroid nodules is important to minimize the number of unnecessary operations.