A new rapid technique for the fixation of thyroid gland surgical specimens.
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One of the main diagnostic problems in thyroid pathology is to distinguish between follicular adenoma and follicular carcinoma. Thorough sampling of the nodule's capsule is recommended in order to identify capsular invasion. However, during the hardening of the tissue, by the usual fixatives the capsule shrinks and rolls downwards and sometimes the capsule separates from the remaining tissue. The present work evaluates the use of "Lymph Node Revealing Solution" (LNRS) for the rapid fixation (2h) of different thyroid lesions as compared to that of formalin. Fifty-one unselected consecutive cases of thyroid nodules, which included various benign and malignant lesions, were examined. Each specimen was cut in two equal parts; one was fixed in LNRS, the other in formalin. Fixation in LNRS for 2 hours gave adequate results in sectioning and staining of the tissue, and excellent immunostains. Its advantage over formalin is the conservation of the natural relationship between the capsule and the rest of the tissue, on the same plane, as well as the short time required for the final diagnosis. (+info)
Promoting effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone on rat glandular stomach carcinogenesis initiated with N-methyl-N'-nitro-N-nitrosoguanidine.
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The modifying effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a mutagenic by-product in chlorinated water, on the development of glandular stomach cancers were investigated in Wistar rats. A total of 120 males, 6 weeks of age, were divided into six groups. After initiation with 100 ppm N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) solution and 5% NaCl diet for 8 weeks, 30 rats each in groups 1-3 were given MX in the drinking water at concentrations of 30, 10, or 0 ppm for the following 57 weeks. Ten animals each in groups 4-6 were administered the MX without prior carcinogen exposure. There were no statistical significant differences in final body weights between the groups. The incidences and multiplicities of adenocarcinomas in the glandular stomachs were significantly higher (P < 0.05) in the initiated 30 ppm MX group than those in the MNNG/NaCl group. The incidences of atypical hyperplasias in the glandular stomachs were also significantly increased (P < 0.05 or 0.01) by the MX treatments. With their multiplicity, the effects were clearly dose dependent. Interestingly, the 30 ppm MX alone itself induced atypical hyperplasias in the pylorus, although the incidences and severity were low. Moreover, MX showed a tendency to enhance the development of intrahepatic cholangiocellular tumors and thyroid follicular cell tumors in the MNNG-treated animals. The results of the present study thus indicate that MX exerts promoting effects when given during the postinitiation phase of two-stage glandular stomach carcinogenesis in rats. (+info)
DNA copy number changes in thyroid carcinoma.
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The genetic changes leading to thyroid cancer are poorly characterized. We studied DNA copy number changes by comparative genomic hybridization (CGH) in 69 primary thyroid carcinomas. In papillary carcinoma, DNA copy number changes were rare (3 of 26, 12%). The changes were all gains, and they were associated with old age (P = 0.01) and the presence of cervical lymph node metastases at presentation (P = 0.08). DNA copy number changes were much more frequent in follicular carcinoma (16 of 20, 80%) than in papillary carcinoma (P < 0.0001), and follicular carcinomas had more often deletions (13/20 versus 0/26, P < 0.0001). Loss of chromosome 22 was common in follicular carcinoma (n = 7, 35%), it was more often seen in widely invasive than in minimally invasive follicular carcinoma (54% versus 0%, P = 0.04), and it was associated with old age at presentation (P = 0.01). In three of the four patients with follicular carcinoma who died of cancer, the tumor had loss of chromosome 22. DNA copy number changes were found in 5 (50%) of the 10 medullary carcinomas studied. Four of these five carcinomas had deletions, and in two of them there was deletion of chromosome 22. Eleven (85%) of the thirteen anaplastic carcinomas investigated had DNA copy number changes, of which five had deletions, and one had deletion of chromosome 22. The most common gains in anaplastic carcinoma were in chromosomes 7p (p22-pter, 31%), 8q (q22-qter, 23%), and 9q (q34-qter, 23%). We conclude that DNA copy number changes are frequent in follicular, medullary, and anaplastic thyroid carcinoma but rare in papillary carcinoma when studied by CGH. Loss of chromosome 22 is particularly common in follicular carcinoma, and it is associated with the widely invasive type. (+info)
Relationship among 201T1 uptake, nuclear DNA content and clinical behavior in metastatic thyroid carcinoma.
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A prospective study of 201TI uptake was performed to compare 201TI uptake with nuclear deoxyribonucleic acid (DNA) content and clinical behavior of tumors in metastatic thyroid carcinoma and to assess the significance of 201TI uptake in evaluating clinical characteristics of thyroid carcinoma. METHODS: Fifty-six patients with metastases of differentiated thyroid carcinoma had 201TI scintigraphy. Grade of 201TI uptake was semiquantitatively assessed according to tumor-to-background ratio on 2-h late scan. Nuclear DNA content was analyzed within 3 wk of 201TI study by flow cytometry using biopsy material and was classified as diploidy or aneuploidy. Patients were followed up to examine incidence of tumor growth and/or anaplastic transformation. RESULTS: DNA content was diploidy in 48 patients and aneuploidy in 8 patients. 201TI uptake in the DNA-aneuploid group (2.61 +/- 0.29) was significantly higher than that in the DNA-diploid group (1.82 +/- 0.35, P < 0.01 for both groups). Tumor growth was observed in all patients with DNA aneuploidy but in only 5 of 48 patients with DNA diploidy (P < 0.01). Anaplastic transformation was observed in 3 patients in the DNA-aneuploid group but in none of the patients in the DNA-diploid group. CONCLUSION: High 201TI uptake indicates greater incidence of abnormal DNA content with aggressive clinical behavior of metastatic tumors. Thus, 201TI scintigraphy may be useful in characterizing metastatic thyroid carcinoma and in identifying those patients with poorer prognoses. (+info)
Case-control study of thyroid cancer in Northern Italy: attributable risk.
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BACKGROUND: The percentage of thyroid cancer cases attributable to specific risk factors can be calculated to focus preventive strategies. The per cent population attributable risks (PAR) for thyroid cancer were estimated in relation to history of benign thyroid diseases, history of radiotherapy, residence in endemic goitre areas and selected indicators of a poor diet, using data from a case-control study conducted between 1986 and 1992 in Northern Italy. METHODS: Cases were 399 histologically confirmed incident thyroid cancers and controls were 617 patients, admitted to hospital for a wide range of acute, non-neoplastic, non-hormone-related diseases. The PAR were computed on the basis of multivariate odds ratios (OR) and on the distribution of risk exposure among cases, assuming they are representative of the general population of cases. RESULTS: A history of benign thyroid disease accounted for 18.9% of cases, radiotherapy for 1.2%, residence for > or =20 years in endemic goitre areas for 2.4% of cases, and their combination for 21.7% of thyroid cancer cases; selected indicators of a poor diet accounted for 40.9% of thyroid cancer cases in this population. The combination of all factors considered explained over 57% of thyroid cancer cases in both sexes. The estimates for thyroid-related conditions were higher in women than men, whereas the opposite was true for dietary indicators. The overall PAR were somewhat higher in people aged > or =45 years (63.8%) than in younger subjects, and for follicular (69.1%) rather than papillary (53.7%) cancers. CONCLUSIONS: Exposure to a few simply identified and potentially modifiable risk factors or indicators (benign thyroid disease, residence in endemic goitre area and a poor diet) explained about 60% of thyroid cancer cases in this Italian population, indicating the theoretical scope for prevention. (+info)
Reproductive and hormonal risk factors for thyroid cancer in Los Angeles County females.
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We conducted an individually matched case-control study (292 pairs) of female thyroid cancer patients to examine the role of reproductive history and exogenous hormones in this disease. Radiation treatment to the head or neck [28 cases and 2 controls exposed; odds ratio (OR), 14.0; 95% confidence interval (CI), 3.5-121.3] and certain benign thyroid diseases (including adolescent thyroid enlargement, goiter, and nodules or tumors) were strongly associated with thyroid cancer. Irregular menstruation increased risk (OR, 1.8; 95% CI, 0.9-3.7). Age at menarche and pregnancy history were not related to disease. Women with natural menopause and hysterectomized women without oophorectomy had no increase in risk, but disease risk was elevated in women with bilateral oophorectomy (OR, 6.5; 95% CI, 1.1-38.1). In general, use of oral contraceptives and other exogenous estrogens was not associated with thyroid cancer. However, risk increased with number of pregnancies in women using lactation suppressants (P = 0.03) and decreased with duration of breastfeeding (P = 0.04). These data provide only limited support for the hypothesis that reproductive and hormonal exposures are responsible for the marked excess of thyroid cancer risk in adult females. (+info)
Non-suppressed thyrotropin and elevated thyroglobulin are independent predictors of recurrence in differentiated thyroid carcinoma.
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OBJECTIVE: Although in most cases differentiated thyroid carcinoma (DTC) responds to surgery and radioiodine (RaI) therapy, some patients will have recurrence and eventually cancer-related death. However, although various prognostic factors of DTC have been identified (e.g. staging, suppressed thyrotropin), none of the previous studies have assessed simultaneously their role in multivariate analysis. DESIGN AND METHODS: In this retrospective population-based study, we reviewed the clinicopathological data of 254 DTC patients treated in eastern Finland during the years 1976-1995, for clinical characteristics, primary treatment, follow-up and cancer recurrence. Tumor stage was based on pathological tumor-node-metastasis (pTNM) classification, and histopathological specimens were re-evaluated. RESULTS: DTC recurrence occurred in 33 patients (13%). In univariate analyses, the predictors of recurrence were older age (>60 years, P<0.05), follicular tumor type (P<0.01), pTNM classification system (P<0.05) and post-ablative radioiodine uptake outside the neck (P<0.05). Non-suppressed serum thyrotropin (TSH) and elevated serum thyroglobulin (>3 microg/l) measured one year after operation were both related to tumor recurrence (P<0.05 and P<0.001 respectively). In multivariate analysis the independent predictors for recurrence were both elevated thyroglobulin (P<0.001) and non-suppressed TSH (P<0.05) independent of histology, pTNM stage and RaI uptake. Adjusted risk ratio for recurrence of DTC for unsuppressed thyrotropin was 2.3, for elevated thyroglobulin 14.0 and, if both conditions were present, the risk ratio increased to 45.1. CONCLUSION: Our results suggest that both non-suppressed serum TSH and elevated serum thyroglobulin are related to an increased risk of DTC recurrence independent of tumor type and pTNM stage. (+info)
Expression of cytokeratin 20 in thyroid carcinomas and peripheral blood detected by reverse transcription polymerase chain reaction.
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We investigated a nested reverse transcriptase polymerase chain reaction (RT-PCR) system to detect CK20 mRNA in thyroid carcinomas, benign thyroid diseases and peripheral blood to improve diagnosis of thyroid carcinoma and to detect disseminated tumour cells. Frozen tissue samples of 46 thyroid carcinomas and 30 benign thyroid diseases (14 multinodular goiters, 14 follicular adenomas, two Hashimoto's thyroiditis) were obtained intraoperatively. Preoperative blood samples were drawn from 31 patients with thyroid cancer, nine patients with benign thyroid disorders and 20 healthy volunteers. Nine out of nine medullary, 9/12 follicular, 7/19 papillary and 2/6 anaplastic carcinomas expressed CK20 transcripts. CK20 mRNA was undetectable in 30 tissue sections of benign thyroid diseases. Circulating tumour cells were found in the blood of 3/8 patients with medullary carcinoma, 2/8 patients with follicular carcinoma, 2/11 patients with papillary carcinoma and 1/4 patients with an anaplastic carcinoma. Nine blood samples of patients with benign thyroid diseases and 20 healthy volunteers tested negative. For the first time CK20 mRNA could be detected in tissue sections of thyroid carcinomas and peripheral blood samples of patients with thyroid cancer. It was not detectable in benign thyroid diseases. Our results therefore strongly suggest that CK20 RT-PCR assays may improve the diagnosis of thyroid carcinoma and is able to detect circulating tumour cells in peripheral blood of thyroid carcinoma patients. (+info)