EXPERIMENTAL cancer of the thyroid.
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Neoplasms↗
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The treatment of thyroid cancer. The role of fine-needle aspiration cytology.
A series of 960 fine-needle aspiration biopsies of thyroid lesions are reported. The primary indication is the presence of a solitary thyroid mass. Aspiration biopsy is accomplished using a 23-gauge needle and a commercially available syringe pistol equipped with a 20.0-mL syringe. Sensitivity for the presence of a thyroid neoplasm, specificity for the absence of a thyroid neoplasm, predictive value of a positive diagnosis for a thyroid neoplasm, and diagnostic efficiency are all over 90% in this series. Eight percent of the aspirates were unsatisfactory. Use of fine-needle aspiration biopsy for the diagnosis of thyroid conditions reduces thyroid surgery significantly for nonneoplastic disease. It is cost-effective and essentially free of complications.
Biopsy, Needle↗
[Breast neoplasms and thyroid therapy].
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Breast Neoplasms↗
Genetic Changes in Chromosomes 1p and 17p in Thyroid Cancer Progression.
Little is known about the genetic alterations that occur during the progression of thyroid neoplasms. To understand better the biology of thyroid tumors, we investigated several genetic loci in benign and malignant thyroid neoplasms. Forty-one thyroid tumors (6 adenomas, 16 papillary, 14 follicular, and 5 anaplastic carcinomas) were studied. Normal and tumor cells were microdissected from paraffin-embedded tissues. DNA was used for polymerase chain reaction-based loss of heterozygosity (LOH) analysis with the following markers: D1S243 (1p35-36), D1S165 (1p36) and D1S162 (1p32), TP53 (17p13), and INT-2 (11q13). Immunohistochemistry for Ki-67 was performed. The Ki-67 labeling index (LI) was the percentage of positive tumor cells. LOH at 1p was seen in 2 of 5 (40%) informative cases of anaplastic carcinoma (2 of 2 at D1S162 and 1 of 2 at D1S165) and in 2 of 11 (18%) informative cases of follicular carcinoma (2 of 7 at D1S243, 2 of 7 at D1S1654, and 1 of 6 at D1S162). One anaplastic (20%) and two follicular carcinomas (14%) had LOH in at least two of the 1p loci analyzed. None of the adenomas and papillary carcinomas had LOH at these loci. LOH at 17p and 11q13 were infrequent. Ki-67 LI was 1.4, 7, 16, and 65% in adenomas, papillary, follicular, and anaplastic carcinomas, respectively. Allelic loss at 1p may occur in aggressive types of thyroid carcinoma and may be a marker of poor prognosis. LOH at 1p may represent a late genetic event in thyroid carcinogenesis. LOH at 17p and 11q13 (MEN gene locus) is uncommon in thyroid neoplasms.
Journal Article↗
Clinical and genetic analysis of an inherited case of thyroid adenoma/cancer.
We studied a family in which thyroid neoplasms appeared to occur through genetic inheritance. Six blood relations, including the two probands, had thyroid carcinoma, and six others had benign thyroid tumors. When both parents had a thyroid neoplasm, their children frequently had thyroid neoplasms; this was confirmed through two generations of this family. To clarify the mechanism of inheritance, we performed chromosomal analysis, Southern blot analysis of three variable number of tandem repeats markers and HLA typing on two probands, and examined their RET proto-oncogenes, and p53 and RB tumor suppressor genes. We could not find any positive data on genetic analysis, although our data were limited. In conclusion, we studied a family in which thyroid neoplasms have occurred partly through genetic inheritance, although environmental factors may have influenced the occurrence of thyroid diseases. A search for a predisposing gene, using the microsatellite technique, is required to clarify the gentic factors involved.
Adenoma↗
Thyrotrophin receptors in normal and neoplastic (primary and metastatic) canine thyroid tissue.
Thyrotrophin (TSH) is the conditional growth factor of thyroid epithelial cells. Abnormalities in TSH-receptor binding such as a low receptor number or low binding affinity may be a marker of thyroid carcinoma or metastases, or may exhibit a relationship with the functional variability of such tissues. The dog was used as a model to characterize TSH-receptor binding in normal thyroid tissues, naturally occurring thyroid neoplasms and distant metastases. In normal dog thyroid tissues, specific 125I-labelled TSH binding ranged from 2.7 to 15.5%, and low cross-reactivity with bovine LH (0.023%) was observed. One class of TSH-binding sites was found in eight normal thyroid tissues and 22 thyroid carcinomas; two normal thyroid tissues and one tumour exhibited two classes of binding sites. The concentration of binding sites was lower in the five carcinomas with reduced pertechnetate uptake (0.09 pmol/mg protein) than in the five thyroid neoplasms with increased uptake (0.19 pmol/mg) (P = 0.055). Compared with the original carcinoma tissues, TSH binding revealed a reduced binding affinity in eight out of eleven metastases. Two metastases showed a complete absence of TSH binding, suggesting that they were not dependent on TSH for growth. We conclude that one class of TSH-binding site is predominant in normal dog thyroid tissues and dog thyroid carcinomas. TSH could therefore contribute, at least in theory, to further growth of primary dog thyroid carcinomas. Secondly, assays measuring TSH binding may not be able to discriminate between malignant and benign dog thyroid tumours. TSH receptor number or affinity may be related to the functional variability of thyroid neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Second primary neoplasms in thyroid cancer patients.
To determine risk patterns for second primary neoplasms after the occurrence of thyroid cancer, we conducted a retrospective cohort study of 3321 thyroid cancer patients who were operated and histologically confirmed at the Noguchi Thyroid Clinic and Hospital Foundation between 1946 and 1985. They were followed from the date of operation through the end of 1990 with an observation period from 45 to 5 years. The average observation period of the patients was 13.4 years and the follow-up rate reached 98%. The standardized mortality ratio (SMR) was computed to assess possible risk increase by cancer site. In this computation, the time period less than 5 years after operation was omitted to reduce the influence of deaths related to the original thyroid cancer. A total of 103 deaths from malignant neoplasms other than thyroid cancer were observed during this time period (SMR = 1.6, 95% confidence interval [CI] = 1.3-2.0). Analyses of site-specific cancer mortality revealed significantly elevated risks for the central nervous system (SMR = 16.1, CI = 5.2-37.6) and respiratory organs (SMR = 2.6, CI = 1.5-4.1). Based on a review of available medical records with histological findings, we concluded that the risk increases for these sites were most likely to be attributable to second primary neoplasms. Whether or not the patients had received radiotherapy was not significantly associated with elevated risk. Further investigations are needed to clarify the risk factors responsible for the above findings.
Adolescent↗
Immunocytochemical detection of p53 in human thyroid carcinomas is associated with mutation and immortalization of cell lines.
Mutations in the tumor suppressor gene p53 are the most-common mutations found in human cancers. In thyroid cancers, p53 mutations generally are found only in poorly differentiated and undifferentiated tumors and in cell lines. To determine the prevalence of p53 mutations in thyroid neoplasms and thyroid cell lines, we screened 58 thyroid tissues and 3 thyroid cell lines, p53 primers bracketing exons 4, 5/6, 7, and 8 were used to amplify genomic DNA using the PCR. Mutations were screened by denaturing gradient gel electrophoresis and confirmed by sequencing. The two papillary thyroid cancer cell lines and the follicular thyroid carcinoma cell line (positive control) had transitions (CGT->CAT) in exon 8, codon 273, resulting in the replacement of arginine with histidine. No normal thyroid tissues or primary tumors from which the cell lines were derived demonstrated exon 8 mutations, using this technique. p53 immunocytochemistry demonstrated a progression of p53 immunopositivity between synchronous and metachronous neoplasms, paralleling the neoplastic progression from a benign adenoma to primary carcinoma, regional, and distant metastasis and ultimately, the cell lines, where intense immunopositivity is noted. In addition, fluorescence in situ hybridization, using probes specific for the p53 locus, revealed the presence of 3 homologues of p53 in the follicular cell line and 2 homologues in the papillary and Hürthle cell lines. These results suggest that a point mutation present in a small number of original tumor cells and amplification of the mutant allele may be responsible for immortalizing well-differentiated thyroid cancer cells into cell lines.
Adenocarcinoma, Follicular↗
Computer-assisted cell morphometry and ploidy analysis in the assessment of thyroid follicular neoplasms.
Conventional cytology cannot discriminate between benign and malignant follicular neoplasms. Our study evaluated the diagnostic role of computer-assisted image analysis in the presurgical assessment of thyroid follicular neoplasms. Fifty-eight patients (14 males, 44 females, age range, 45-75 years) who underwent surgery for cytologic diagnosis of thyroid follicular neoplasm were studied. All patients were first evaluated on clinical grounds and assigned a high/low suspicion of malignancy on the basis of gender, age, and nodule size. Cell image analysis was subsequently performed using a Cytometrica BYK Gulden microscope image processor on Feulgen-stained thyroid cytologic smears. A different population of 50 benign and 50 malignant, histologically evaluated nodules was studied in order to establish image analysis criteria suggestive of thyroid malignancy. Ploidy histogram, proliferation index (PI), nuclear area coefficient of variation (NACV), and anisocariosis ratio (AR) were studied. Thyroid cancer was diagnosed in 16 of 58 follicular neoplasms. Only 7 of these lesions were clinically suspicious (43.7%), whereas 14 of 16 (87.5%) malignant tumors were identified by image analysis. Positive and negative predictive values of image analysis versus clinical evaluation were 46.6% versus 30.4% and 92.8% versus 74.3%, respectively. The distribution of ploidy pattern was different in benign versus malignant follicular neoplasms (chi2 8.25, p = 0.016), malignant lesions showing an increased frequency of heteroclonal aneuploid DNA content (37.5% vs. 7.1%). Increased PI (mean +/- standard deviation (SD) = 11.3 +/- 5.7 vs. 7.1 +/- 6.1; p < 0.01) and NACV (mean +/- SD = 25.28 +/- 1.89 vs. 20.14 0.91; p < 0.01) levels were also observed in malignant follicular neoplasms. In conclusion, computer-assisted image analysis may profitably support clinical evaluation in the assessment of thyroid follicular neoplasms.
Adenoma↗
[Tumor markers for endocrine neoplasms].
Tumor markers for thyroid neoplasms include thyroglobulin, calcitonin, and CEA. Thyroglobulin is particularly useful in discriminating follicular carcinoma from its benign counterparts. The measurement may also be helpful in the postoperative follow-up of patients with either follicular carcinoma or papillary carcinoma. Measuring plasma calcitonin and CEA is essential in the diagnosis and postoperative management of patients with medullary carcinoma. Highly specific genetic tests may become an alternative strategy in cases of familial medullary carcinoma. No specific tumor markers are available for parathyroid carcinoma; however, clinical characteristics provide diagnostic clues.
Biomarkers, Tumor↗
[Recurrent thyroid gland neoplasms].
The data on 106 patients with thyroid cancer recurrence are reported. The recurrences occurred in the zone of surgery in 76.4%, beyond this zone--in 23.6%. During a 3-year period the recurrence occurred in 41.5%, from 3 to 10 years - in 44.4%, after 10 years and longer - in 14.1%. One of the main causes of the recurrence is an inadequate extent of primarily performed surgery. The recurrent tumor was detected by palpation, regional metastases were detected in 47.1%, distant--in 22.6%. A lower differentiation of the recurrent tumor was noted. The combination treatment was employed in 64% of patients. The principal surgical procedures were as follows: total thyroidectomy and subtotal thyroidectomy.
Adult↗
Sentinel lymphadenectomy in thyroid malignant neoplasms.
BACKGROUND: Lymph node metastases for well-differentiated thyroid cancer are associated with high recurrence rates. Surgical options consist of blind nodal sampling, "berry-picking" procedures, and modified radical neck dissections. Sentinel lymph node dissection (SLND) has been described by our institution for melanoma and breast cancer. We have investigated the feasibility of SLND for thyroid cancer. DESIGN: From August 1994 to October 1996 we investigated the technique of intraoperative lymphatic mapping and SLND in 17 patients undergoing surgical management of a suspicious thyroid nodule not accompanied by palpable cervical adenopathy. SETTING: Patients were referred from endocrinologists in community and academic practices. Procedures were performed in a community hospital. PATIENTS: There were 14 women and 3 men, ranging in age from 22 to 69 years (median, 48 years). INTERVENTIONS: At surgery, we exposed the thyroid lobe and used a tuberculin syringe to inject 0.1 to 0.8 mL of 1.0% isosulfan blue dye (mean, 0.5 mL) directly into the thyroid mass. Within seconds the blue dye passed along the lymphatics to the sentinel lymph node, which was then excised. Nodes were examined by routine processing and keratin immunohistochemical analysis to detect micrometastasis. MAIN OUTCOME MEASURES: The feasibility of lymphatic mapping in determining primary drainage of suspicious thyroid nodules. RESULTS: Lymphatic mapping and SLND was followed by total thyroidectomy, except in 1 patient who underwent lobectomy for benign disease. Of the 17 nodules, 12 were ultimately diagnosed as thyroid carcinoma, 3 were follicular adenomas, and 2 were colloid nodules. Tumor sizes ranged from 0.8 to 4.0 cm. Lymphatic mapping was unsuccessful in 2 patients, whose lymphatics mapped to the retrosternum. All of the sentinel lymph nodes were paratracheal except in 2 women who also had jugular nodes that stained blue. Five (42%) of the 12 tumor nodules were associated with positive sentinel lymph nodes. Central neck dissections were performed in 5 patients; in 2 instances (17%), the sentinel node was the only tumor-bearing lymph node. CONCLUSIONS: This is the first report of SLND for thyroid carcinoma. Our preliminary findings indicate that SLND can detect nonpalpable nodal metastasis with the same ease as in melanoma and breast cancer. The clinical significance of this technique in thyroid cancer remains to be determined.
Adult↗
Prognostic factors in patients with Hürthle cell neoplasms of the thyroid.
BACKGROUND: Hürthle cell neoplasms, often considered a variant of follicular thyroid neoplasms, represent 3% of thyroid carcinomas. Only a handful of publications have focused on the biologic behavior, prognostic factors, and treatment outcomes of Hürthle cell carcinoma. The objective of the current study was to identify the clinical and pathologic features of Hürthle cell carcinomas that predict disease progression or death. METHODS: The authors reviewed medical records of patients who were treated for Hürthle cell carcinoma (HCC) and Hürthle cell adenoma (HCA) at The University of Texas M. D. Anderson Cancer Center from March 1944 to February 1995, including follow-up information. The pathologic diagnosis was confirmed by one of the authors. RESULTS: The authors identified 127 patients with Hürthle cell neoplasms, 89 patients with HCC and 38 patients with HCA. Seven patients with HCC had foci of anaplastic thyroid carcinoma. Survival for this subgroup was worse compared with the overall group and was analyzed separately. The HCC group was significantly older (age 51.8 years vs. age 43.1. years) and had larger tumors (4.3 cm vs. 2.9 cm) compared with the HCA group. No differences were seen in gender or previous radiation exposure. Forty percent of patients in the HCC group died of thyroid carcinoma, whereas no patients in the HCA group died of the disease. There has been no improvement in all-cause and disease specific mortality in the past 5 decades for patients with these neoplasms. Conventional staging systems predicted mortality with minor differences. Of the patients with known metastasis, 38% showed radioiodine uptake. Univariate analysis identified older age, higher disease stage, tumor size, extraglandular invasion, multifocality, lymph node disease, distant metastasis, extensive surgery, external beam radiation therapy, and chemotherapy as factors that were associated with decreased survival. Tumor encapsulation was associated with improved survival. Although radioactive iodine treatment had no overall effect on survival, subgroup analysis showed that patients who received radioactive iodine for adjuvant ablation therapy had better outcomes compared either with patients who did not receive radioactive iodine or with patients who received radioactive iodine as treatment for residual disease. Multivariate analysis indicated that older age and larger tumor size predicted worse survival through an association with worse behaving tumors (multifocal, less encapsulated, and with extraglandular invasion). The decreased survival in patients with lymph node metastases may be explained by its association with distant metastases. The association of extensive surgery, external beam radiation therapy, and chemotherapy with worse survival also disappeared once those factors were analyzed together with other prognostic factors, such as distant metastases. CONCLUSIONS: Several clinical and pathologic prognostic factors were identified in patients with HCC and HCA. Older age and larger tumor size predicted reduced survival. Radioactive iodine therapy may confer a survival benefit when it is used for adjuvant ablation therapy, but not when residual disease is present. The authors could not demonstrate a survival benefit for the use of extensive surgery, external beam radiation therapy, or chemotherapy.
Adenoma, Oxyphilic↗
Fractal dynamics in the differential diagnosis of thyroideal follicular neoplasms.
In this study, we investigated the sensitivity, specificity, and predictive values of morphometric parameters of thyroideal follicular neoplasms based on concepts of fractal geometry. Thirty-seven follicular adenomas and 36 well-differentiated follicular carcinomas were assessed morphometrically. The nuclear area, nuclear area fraction, nuclear regularity factor, nuclear elongation factor, and slope setting (representing the ratio between the nuclear perimeter and nuclear regularity factor) were subjected to fractal dimensions analysis. By univariate analysis, the nuclear area, nuclear area fraction, nuclear regularity factor and slope values discriminate between adenomas and carcinomas. By multivariate analysis, the nuclear area, nuclear area fraction and slope values possess significant discriminatory powers in distinguishing between adenomas and carcinomas. Incorporating the nuclear area, nuclear area fraction, and slope values leads to a discriminatory power with 92% specificity and 83% sensitivity. The reciprocal relationships between the nuclear area, nuclear perimeter, and nuclear regularity factor of the cells of thyroideal adenomas and carcinomas may be expressed by fractal dimensions. Analysis limited to one parameter provides incomplete data. Expressing variations of the nuclear perimeter as a function of the nuclear regularity factor, the slope values constitute an independent attribute that significantly differentiates thyroideal adenomas from carcinomas.
Adenocarcinoma, Follicular↗
Estrogen and thyroid-stimulating hormone (TSH) receptors in neoplastic and nonneoplastic human thyroid tissue.
Estrogen-binding receptors (ER) and thyroid-stimulating hormone (TSH) receptors were observed in the cytosol and in a membrane particulate fraction, respectively, in most neoplastic and nonneoplastic human thyroid tissues. Fourteen of 15 thyroid neoplasms and 6 of 15 nonneoplastic thyroid specimens had estrogen receptors (assuming the sensitivity of our estrogen receptor assay is 0.2 fmole/mg protein), and 14 of 15 thyroid neoplasms and 11 of 15 nonneoplastic thyroid specimens had a high affinity, low capacity TSH receptor. Neoplastic thyroid tissue had more ER (2.35 +/- 0.70/fmole/mg protein) than nonneoplastic thyroid tissue (0.57 +/- 0.181/fmole/mg protein) removed from the same patients (P less than 0.05). The Kd for ER did not differ in nonneoplastic (0.41 +/- 0.090 nM) and neoplastic (0.311 +/- 0.048 nM) thyroid tissue. The number of TSH receptors was comparable in neoplastic (0.609 +/- 0.191 pmole/mg protein) and in nonneoplastic (0.765 +/- 0.181 pmole/mg protein) thyroid tissue removed from the same patients who had the ER studies. The maximal adenylate cyclase response to TSH was greater in the neoplastic (147 +/- 26.9 pmole/mg protein/30 min) than in nonneoplastic thyroid tissue (32.8 +/- 6.69 pmole/mg protein/30 min) (P less than 0.001) suggesting a greater metabolic responsiveness of the neoplastic thyroid tissue to TSH. No correlation was evident, however, between the number of estrogen and TSH receptors in nonneoplastic and neoplastic thyroid tissue (r = 0.226). This study demonstrates that neoplastic human thyroid tissues have both estrogen receptors and TSH receptors. The neoplastic tissue also has a greater AC response to TSH than nonneoplastic thyroid tissue.
Adenocarcinoma↗
Thyroid follicular neoplasms diagnosed by high-resolution ultrasonography with fine needle aspiration cytology.
OBJECTIVE: To investigate the final results of cases with preoperative diagnoses of thyroid follicular neoplasms by fine needle aspiration cytology (FNAC). STUDY DESIGN: A retrospective review of 6,499 patients who received thyroid ultrasonography with FNAC at Chang Gung Memorial Hospital. Among 6,499 patients, 209 (3.2%) were diagnosed by FNAC as having follicular neoplasms, of which 84 received surgical treatment. Eighty-two of the 84 cases had a frozen section prepared during the operation. RESULTS: Thyroid malignancy was confirmed histopathologically in 164 cases. Among 84 thyroid follicular neoplasm patients, 21 cases were diagnosed as malignant tumors, including papillary thyroid carcinoma, follicular thyroid carcinoma, medullary thyroid carcinoma and Hürthle's cell carcinoma. Ultrasonography on these 21 patients revealed that 16 cases (76.2%) had low echo density in the thyroid nodule. The percentage was statistically significantly different from that in benign cases, 23.8% (P < .05). A higher incidence of malignancy was found in males, but the data did not reach statistical significance (P = .0586). CONCLUSION: Most of the follicular neoplasms revealed by FNAC were benign lesions. Low echo density on ultrasonography and male sex carried a higher risk of malignancy.
Adenocarcinoma, Follicular↗
Role of AgNOR in diagnosis of thyroid follicular neoplasms on fine-needle aspiration smears.
This is a retrospective study to examine the role of AgNOR in differentiating thyroid follicular carcinoma and adenoma preoperatively on fine-needle aspiration (FNA) smears. Nineteen histopathology-proven cases of follicular adenoma and carcinoma were selected for this study. May-Grünwald-Giemsa-stained smears were destined and AgNOR staining technique was employed. Significant differences of AgNOR values were observed among follicular carcinoma versus adenoma (P < .05) and follicular carcinoma versus control cases (P < .01). Thereby the AgNOR technique may have some role in differentiating between benign and malignant follicular neoplasms of thyroid.
Adenocarcinoma, Follicular↗