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PubMed2006

Vascularity in thyroid neoplasms: a methodological investigation with a view to diagnostics.

The aim of the present study was to evaluate the reliability of four different methods (vascular grading, Chalkley count, microvessel density (MVD) and stereological estimation) for quantifying intratumoral microvascularity in thyroid neoplasms, by comparing the variability within and between observers. In addition, the diagnostic and prognostic potential of neovascularity expressed by the four methods was evaluated. The study had a retrospective design and involved 24 follicular adenomas (FA), 19 follicular carcinomas (FC), and 17 papillary carcinomas (PC). Chalkley count was reproducible both within and between observers. MVD was not reproducible. Within observer the reproducibility of vascular grading was substantial, between observers it was fair to moderate. Stereological estimation was a priori considered reproducible. Keeping time consumption, cost and reproducibility in mind, Chalkley count should be the preferred method for assessing microvascularity in thyroid neoplasms. The diagnostic evaluation revealed a tendency towards higher degree of vascularity in FA compared to both FC and PC for all methods. No statistically significant association was seen between vascular density and prognosis.

Adolescent↗
PubMed2006

Delta Np73 expression in thyroid neoplasms originating from follicular cells.

AIMS: p73, a homologue of p53, is known as a negative regulator of tumour progression. However, delta Np73, an isoform of p73 lacking the NH2-terminal transactivation domain plays an oncogenic role by interfering with the activity of p53 and TA (full-length transactivating isoforms) p73. In this study, we investigated the expression of delta Np73 in human thyroid neoplasms originating from follicular cells. METHODS: We immunohistochemically investigated delta Np73 expression in 223 thyroid neoplasms. Delta Np73 expression level was evaluated as the sum of positivity score and intensity score. RESULTS: Normal follicular cells did not express delta Np73, but 27.3% of follicular adenoma, 85.4% of follicular carcinoma, 99.2% of papillary carcinoma, and 95.7% of anaplastic carcinoma were positive for the transcript. Delta Np73 expression level did not differ between widely invasive and minimally invasive follicular carcinomas. In papillary carcinoma, the level was inversely linked to tumour size, extrathyroid extension, and clinically apparent metastasis. Furthermore, in anaplastic carcinoma, delta Np73 expression level was significantly lower than that in papillary carcinoma. CONCLUSIONS: Our findings indicate that delta Np73 plays a role predominantly in the early phase of papillary carcinoma progression.

Adenocarcinoma, Follicular↗
PubMed1978

Thyroid neoplasms after radiation therapy for adolescent acne vulgaris.

There is a potential hazard of thyroid cancer after exposure to external irradiation for the treatment of adolescent acne vulgaris. We noted a 60% incidence of thyroid carcinoma among 20 patients with such a history, who were operated on for thyroid nodules during a five-year period. Eighty-three percent of the patients with carcinoma had either a follicular or a mixed papillary-follicular carcinoma; 17% had a papillary carcinoma; 33% had regional node metastases; none had evidence of distant metastases. The interval between radiation exposure and thyroidectomy ranged from nine to 41 years. This association of thyroid neoplasms and a prior history of radiation for acne vulgaris may be coincidental and therefore remains to be proved by retrospective surveys of large numbers of treated patients with appropriate controls.

Acne Vulgaris↗
PubMed1995

[Evaluation of blood-group-related carbohydrate antigens in thyroid neoplasms].

An immunohistochemical study using a panel of monoclonal antibodies (mAbs) against blood group A, B, H and Lewis antigens Le(a), Le(b), Le(x) and Le(y) and lectins, such as PNA, VVA-B4 and UEA -1, was carried out to investigate the aberrant expression of carbohydrate antigens in formalin-fixed, paraffin-embedded tissue sections of thyroid neoplasms. The tissues examined consisted of 26 papillary carcinomas, seven follicular adenomas, seven follicular carcinomas, one anaplastic carcinoma and one medullary carcinoma. MAbs against A, B and H antigens reacted strongly with papillary carcinomas from most of the individuals studied (22 of 26 individuals) and their reactivity corresponded well to the blood groups of individuals. In follicular adenomas and carcinomas, these mAbs reacted weakly with a small number of neoplastic cells from two of seven, and four of seven individuals, respectively. Positive staining with mAbs against Le(a) and Le(b) antigens was found in almost all papillary carcinomas. On the contrary, these mAbs rarely reacted with cells from follicular adenomas and carcinomas. T and Tn antigens which were recognized by PNA and VVA-B4, respectively, were only weakly expressed in a limited number of cells from the thyroid neoplasms. Normal cells adjacent to malignant cells were not stained by any of the stains used in this study. These results are discussed in light of our recent findings that polylactosamine structures produced in papillary carcinomas are quite different from those expressed in other types of neoplasms.

Adenocarcinoma, Follicular↗
PubMed1989

Thyroid neoplasms in a colony of beagle dogs.

The histologic, clinicopathologic, and epidemiologic features of spontaneous thyroid neoplasms were evaluated in a control population of Beagle dogs. The mean age of thyroid tumor-bearing dogs (16.2 years) as significantly higher than non-tumor-bearing dogs (13.6 years). Thirteen benign and 18 malignant tumors were identified, with the incidence of both tumors increasing rapidly near the mean age of 16.2 years for tumor-bearing dogs. The age-specific incidence of tumors was 1.1% per year at 8 to 12 years, increasing to 4.0% per year by 12 to 15 years and 67% over 17 years of age. Numbers of malignant tumors were greater than benign tumors at an earlier age. Approximately 44% of the malignant tumors metastasized but only 22% resulted in death of the dog. There was no difference in tumor incidence when compared according to sex, if total tumor numbers were considered or if tumors were separated into benign and malignant categories. The age at death of tumor-bearing dogs was not increased significantly by the surgical resection of the thyroid tumors. Of dogs with thyroid tumors, 15% had clinical diagnoses of hypothyroidism, and no dogs with thyroid tumors had diagnoses of hyperthyroidism.

Age Factors↗
PubMed2005

[DNA content analysis in thyroid neoplasms: diagnostic and prognostic interest].

Thyroid nodules are frequent and sometimes they pose a diagnostic and prognostic problem. DNA ploidy study and cell cycle analysis could be of value in the distinction between benign tumors and malignant tumors. Formalin-fixed and paraffin-embedded tissues from 69 patients with different benign and neoplastic lesions were investigated. Nuclear DNA content in thyroid cells was measured after Feulgen staining using SAMBA 200 image analysis system. A diploid DNA stemline was revealed in 75% of histologically proven benign thyroid tumors (15/20) and aneuploidy was found in 57.2% of malignant tumors (28/49). There is a significant correlation between aneuploidy and extra-thyroid extension (p=0.007) and bilateral and/or mediastinal lymph node metastasis (p=0.02). In the majority of benign tumors (19/20), the proliferation index was lower than 3% (< or =3%) however, this index value was higher than 3% (>3%) in more than 83% of malignant tumors (41/49) (p<0.001). The S phase fraction analysis revealed that the threshold of 14% divide the near whole of benign and malignant tumors (p<0.001). Our findings show that in follicular lesions, proliferation index and S phase fraction study appears interesting and helpful in the distinction between benign and malignant tumors, and aneuploidy seems more interesting in prognosis evaluation of these tumors.

Aneuploidy↗
PubMed1997

[Personal observations for diagnosis and radical surgical treatment of thyroid neoplasms].

Among 59 patients with thyroid cancer, we have analysed the diagnostic procedures as: ultra sonography, scintiscan, fine needle aspiration biopsy, intraoperative frozen section examination and extent of surgery. The cancer was often overlooked in patients with multinodular goitre. We suggest to perform total lobectomy on side with greater changes and subtotal lobectomy on the other side of thyroid gland, in patients with multinodular goitre. The decision whether to reoperate should depend on the final pathology report.

Adenocarcinoma, Follicular↗
PubMed2005

Thyroid neoplasms in Tikur Anbessa Hospital, Addis Ababa: a retrospective review with emphasis on cancer.

Reportedly, thyroid cancer is a rare disease in most parts of the world. In Ethiopia, the prevalence of the disease is not known. This study aims to present the experience on thyroid cancer of a main central referral hospital. During the period 1993-02, 137 cases of thyroid neoplasms were operated on in Tikur Anbessa Teaching Hospital, Addis Ababa. Of these, 114 of 130 patients whose records were retrieved were retrospectively reviewed Neoplastic disease of the thyroid was found to be more common in younger age groups (mean age, 37 years) and in females (F: M ratio, 1.7: 1.0). Features of advanced malignant disease were not rare (21 cases). Of the 75 thyroid cancers, papillary carcinoma was the most common histologic type (72%). The extent of surgical treatment included partial, subtotal, near total and total thyroidectomy. In 15 cases, the lesions were found to be unresectable. The long-term outcome of treatment was difficult to evaluate, as the follow-up time was short. We believe that this paper will give base-line information on the frequency of thyroid cancer (7.5%) for a more comprehensive study in the future.

Adolescent↗
PubMed2003

Serum thyroglobulin as a marker of thyroid neoplasms after childhood cancer.

AIM: To evaluate serum thyroglobulin (Tg) level as a marker of the development of thyroid disease when following individuals who received neck irradiation therapy in childhood. METHODS: In a non-randomized cross-sectional study Tg was assessed in 172 survivors of childhood cancer 10.8 y (1.9-24) median (range) after diagnosis and 7.9 y (0.9-24.3) median (range) after the end of treatment. The patients were divided into two groups: group 1 included 47 patients who had received irradiation to the neck and group 2 included 125 patients who did not receive irradiation to the neck. RESULTS: Patients who had received irradiation to the neck had significantly higher Tg levels compared with those who did not receive neck irradiation: median 14.0 (1.0-189.0) microg/L vs median 8.8, (0.7-112.2) microg/L (p < 0.001). Six out of seven patients with elevated Tg levels (>70 microg/L) had received neck irradiation. Among these six patients, two patients developed secondary differentiated thyroid cancer and two patients developed benign thyroid neoplasms. None of the patients who had normal levels of Tg developed thyroid cancer. CONCLUSION: A high Tg level should be a cause for further investigation in the follow-up of individuals who have received irradiation therapy in childhood.

Acute Disease↗
PubMed2003

Differences in glycosylation of intracellular proteins between benign and malignant thyroid neoplasms.

Differences in glycosylation of nuclear and cytosolic proteins isolated from benign and malignant human thyroid neoplasms were analyzed by lectin blotting and enzyme linked lectino-solid-phase assay using Erythrina cristagalli and Ricinus communis agglutinins. The results reported in this study have not shown any significant differences in lectin binding by nuclear proteins of benign and malignant tumors, however, quantitative and qualitative differences were observed in the patterns of cytosolic glycoproteins. In the majority of carcinomas samples lectin binding to cytosolic proteins was definitely weaker in comparison with adenomas and non-neoplastic specimens, which suggested alterations in glycosylation of cytosolic proteins in malignant tumors.

Adolescent↗
PubMed1999

Classification and treatment of follicular thyroid neoplasms are discordant between and within medical specialties.

BACKGROUND: The histologic criteria to classify follicular thyroid neoplasms are controversial. Criteria used for diagnosis and treatment varies both within and between specialty groups. This discordance makes it difficult to compare disease and management practice. This is especially problematic in issues concerning reoperations and survival. To determine the degree of disparity, we surveyed 3 groups of specialists. METHODS: A questionnaire describing 10 histologic scenarios was sent to an equal number of thyroidologists, endocrine surgeons, and endocrine pathologists. Individuals were randomly selected from rosters of 3 corresponding societies. Each item asked for a rating of a diagnosis and treatment. Questionnaires were distributed and received by facsimile, and responses were kept confidential. The response rate was 60%. RESULTS: Responses were analyzed by nonparametric statistical tests. Two scenarios had significant disagreement among specialties in both diagnosis and treatment: one scenario involved the assessment of neoplasms with minimal capsular invasion; the other scenario involved Hürthle cell features. In both scenarios pathologists tended to be more conservative in assigning the term carcinoma and recommending total thyroidectomy. Significant disagreement within specialty groups was also noted. Two other scenarios dealt with the distinction between minimally and widely invasive carcinoma; significantly, pathologists viewed tumors as less invasive. CONCLUSIONS: This study indicates that much disparity exists among specialists in pathology, endocrinology, and surgery and among experts in each of these disciplines. It highlights that there is no uniform classification. If multicenter trials to evaluate treatment options are to occur, a universal classification must be accepted.

Adenocarcinoma, Follicular↗
PubMed1990

H-ras protooncogene mutations in human thyroid neoplasms.

Structural alterations of protooncogene sequences may be involved in the pathogenesis of human neoplasms. We screened 54 thyroid tumors (36 benign and 18 malignant) for gene rearrangements of the protooncogenes c-myc, c-myb, c-fos, c-erb-B1, c-erb-B2, c-erb-A, N-ras, K-ras, and H-ras. Only mutations of H-ras were observed. None of the 15 colloid adenomas examined had detectable H-ras rearrangements. Of the remaining tumors, we observed mutations of H-ras in 4 benign and 4 malignant neoplasms. Gene amplification was found in 5 tumors. An aggressive recurrent papillary carcinoma had a marked amplification of one of the H-ras alleles. The amplified allele was truncated, in that the 3' variable tandem repeat was not a part of the amplification unit, and contained a codon 12 point mutation leading to a valine for glycine substitution. We also observed the association of low copy gene amplification with a codon 12 valine for glycine mutation in a follicular adenoma. Two tumors contained H-ras EcoRI polymorphisms not present in the DNA of normal thyroid from the same individuals, and one follicular carcinoma showed loss of an H-ras allele. Ras protooncogenes may become transforming by quantitative mutations, leading to increased expression, or qualitative mechanisms, through activating point mutations. Both of these appear to coexist in thyroid neoplasms, and it may be that a combination of both mechanisms is capable of inducing a more complete spectrum of neoplastic phenotypes.

Base Sequence↗
PubMed1990

Frequency and degree of aneuploidy in benign and malignant thyroid neoplasms.

The frequency and degree of aneuploidy in 44 benign and 124 malignant thyroid neoplasms were analyzed by DNA flow cytometry. Single aneuploid cell populations were found in 72% of the undifferentiated carcinomas, 64% of the follicular carcinomas, 24% of the papillary carcinomas and in 24% of the follicular adenomas. Multiple aneuploid cell populations were detected in 4% of the papillary and in 36% of the follicular carcinomas but not in undifferentiated carcinomas. A low degree of aneuploidy was found in well differentiated papillary carcinomas (mean DNA index of aneuploid populations: DI = 1.17; SD +/- 0.09). Significantly higher values were found for aneuploid moderately differentiated papillary carcinomas (DI = 1.46; SD +/- 0.29), well and moderately differentiated follicular carcinomas (DI = 1.61; SD +/- 0.33 and DI = 1.60; SD +/- 0.30, respectively) and undifferentiated carcinomas (DI = 1.72; SD +/- 0.19). High DNA indices were also found in several follicular adenomas (DI = 1.49; SD +/- 0.22). Comparison of the 10-year survival rates of patients with moderately versus well differentiated papillary carcinoma (79 vs. 98 months, respectively) indicates that loss of differentiation and progression of aneuploidy in this tumour type is associated with more aggressive clinical behaviour. Similarly, the high frequency and degree of aneuploidy in undifferentiated carcinomas is in agreement with the very poor survival rate (0% at 10 years) in this group of patients. However, the occurrence of highly aneuploid adenomas and (near)-diploid undifferentiated carcinomas does not point to a direct causal relationship between DNA-ploidy changes and clinical behaviour of these thyroid tumours.

Adenocarcinoma↗
PubMed1992

Thyroid neoplasms. Can we do any better with quantitative cytology?

The differential diagnosis of thyroid neoplasms by routine cytology presents major difficulties. We therefore looked for measurable nuclear parameters that could be generated from Feulgen-stained smears obtained by fine needle aspiration biopsy (FNAB). These parameters would then be used to differentiate between benign and malignant lesions. Seventy-six patients whose cold thyroid nodule was surgically excised after FNAB and examined by a pathologist were used in this study: 56 benign, 18 malignant and 2 atypical adenomas. A set of 3,662 cells from the 33 benign cases was compared with the set of 1,712 cells from the 11 malignant nodules. Discrimination between the two populations was based on four nuclear features ranked according to their discriminating power. The first ranked was a textural parameter, followed by a densitometric and finally two other textural parameters. The rate of nuclei that could be regarded as benign was computed for each case using the ranked parameters. The average rate for the 33 benign cases was 85% (50.2 = 100%, set at the 95% confidence interval). In a prospective study of the 32 remaining patients, sensitivity and specificity were, respectively, 92% and 88%, which were higher than those obtained by conventional cytology.

Adenoma↗
PubMed1991

Insulin-like growth factor-II (IGF-II)/Mannose-6-phosphate receptors are increased in primary human thyroid neoplasms.

Insulin-like growth factor (IGF)-II receptors were demonstrated in normal and neoplastic tissues of human thyroid. Specific binding of [125I]IGF-II to thyroid membranes was dependent on the time and temperature of incubation, and a steady state was achieved after 22 h of incubation at 4 degrees C. The binding of [125I]IGF-II was dose-dependently displaced by unlabelled IGF-II with 50% inhibition at an IGF-II concentration of 6 ng/ml. IGF-I had a relative potency of 1% compared to IGF-II, and insulin showed no inhibition at concentrations as high as 2000 ng/ml. Scatchard analysis of the binding data revealed a single class of IGF-II receptor with high affinity. Affinity crosslinking and autoradiography demonstrated the type II IGF receptors. Specific binding of [125I]IGF-II to thyroid papillary cancer tissues (mean [S.D.]13.2[1.3]% per 200 micrograms protein, n = 8) was significantly (P less than 0.01) higher than that to the surrounding normal tissues (4.8 [0.5]%). The binding in follicular cancer and follicular adenoma was also significantly higher than that in the corresponding normal tissues. The higher IGF-II binding to neoplastic tissues was due to an increase in the number of binding sites without any change of affinity. These results suggest that the increased IGF-II receptors may be involved in growth or functions of thyroid neoplasms.

Binding, Competitive↗
PubMed1989

Radiation induced thyroid neoplasms 1920 to 1987: a vanishing problem?

Radiation for benign diseases has been implicated as an etiologic factor in thyroid cancer. From 1930-60, over 2 million children may have been exposed to therapeutic radiation and it is estimated that up to 7% may develop thyroid cancer after a 5-40 year latency. Thyroid stimulating hormone, secondary to radio-induced hypothyroidism, has been implicated as causative in animals. Such data has led to expensive screening programs in high risk patients. Because of a decline in irradiation for benign diseases in children over the last 2 decades, we questioned whether the incidence of radiation induced thyroid neoplasms (RITN) was also decreasing. Twenty-six of 227 patients (11%) with thyroid malignancies seen at our institution from 1974-87 had a history of previous head and neck irradiation. These included 13 papillary, 3 follicular, and 7 mixed carcinomas as well as 2 lymphomas and 1 synovial cell sarcoma. None of these 26 patients had abnormal thyroid function tests at presentation. Mean latency from irradiation to the diagnosis of thyroid cancer was 25.4 years (6-55 year range). Compared to the reported increasing incidence of RITN from 1940-70, there appears to be a significant decrease since 1970. Based on our analysis, the use of expensive screening programs in high risk populations may no longer be warranted. Additionally, the routine use of thyroid replacement in previously irradiated chemically hypothyroid patients is not recommended.

Adolescent↗