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Accuracy of fine-needle aspiration cytology in patients with radiation-induced thyroid neoplasms.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is useful for selecting patients with thyroid nodules for thyroidectomy. Its value in patients who have been exposed to low-dose therapeutic radiation is questionable because these patients have an increased risk of multifocal benign and malignant tumours, and thyroid cancer is common in such patients. METHODS: Between 1960 and 1999, 171 patients with one or more thyroid nodules who had a history of exposure to radiation underwent operation; 49 of these patients had preoperative FNAC. The cytology results in these 49 patients were compared with those of an age- and sex-matched control group of patients with thyroid nodules who did not have a history of radiation exposure. RESULTS: Of those who had been exposed to radiation, six of 20 patients with 'benign' cytology by FNAC and six of 16 patients with 'suspicious' cytology had thyroid cancer. All 13 specimens considered to be malignant on FNAC were indeed malignant. There was a higher rate of false-negative cytological examinations among patients with a history of irradiation that in those without. CONCLUSION: FNAC of thyroid nodules in patients with a history of irradiation is not as accurate as that in non-irradiated patients, primarily because of coexisting occult thyroid cancers.

Biopsy, Needle↗

Human telomerase reverse transcriptase (hTERT) gene expression in FNA samples from thyroid neoplasms.

Identifying a tumor marker that can help distinguish benign from malignant thyroid tumors is crucial, because up to 30% of thyroid fine-needle aspirations (FNA) are diagnosed as 'suspicious' or follicular neoplasm for malignancy. Recently, the detection of human telomerase reverse transcriptase (hTERT) gene expression in thyroid FNA samples has been identified as a promising diagnostic marker in distinguishing benign and malignant thyroid tumors. Twenty-seven FNA samples from thyroid tumors that were suspected to be malignant were collected preoperatively, hTERT gene expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR), and the cytological and histological results were compared. The results demonstrated that 13 (92.8%) of 14 thyroid carcinomas, including eight of eight papillary, three of four follicular, and two of two Hürthle cell thyroid carcinomas have corresponding FNA samples that were positive for hTERT. Meanwhile, eight (61.5%) of 13 benign thyroid nodules, including three of six nodular goiter, two of two Graves' disease, two of two Hürthle cell adenomas, and one of three follicular adenomas were positive for hTERT. In conclusion, hTERT was more prevalent in malignant thyroid FNA samples than in the benign thyroid FNA samples. Notably, the extent of the differences in hTERT expression between benign and malignant follicular thyroid tumors require further investigation. Moreover, further information including semi-quantitative real-time RT-PCR, is required to verify whether hTERT mRNA expression could serve as an adjunctive molecular marker for the preoperative diagnosis of thyroid malignancies.

Adenocarcinoma, Follicular↗

[Multifactorial prognostic analysis in the surgical treatment of well differentiated thyroid neoplasms].

BACKGROUND: Although in recent years our knowledge of pathogenesis and natural history of thyroid cancer has widely increased, there is not accordance among authors in the field of surgical treatment of well-differentiated tumours. In fact the extension of the tumour resection and modality of cervical lymph-nodes dissection show questions not easy to answer. METHODS: From 1985 to 1994, in our Surgical Institute, 128 cases of well-differentiated thyroid cancer, out of 1346 nodular thyreopathies, were operated on. We have considered some factors as anamnestic thyreopathy, familiarity, symptoms, US and scyntigraphic factors, fine-needle aspiration cytology and surgical option. The surgical treatment consisted of 99 total thyroidectomies (with or without cervical lymph-nodes dissection) and 18 lobus-isthmectomies. Surgical morbidity was 0.7% for permanent vocal cords palsy, 9.3% for transient hypoparathyroidism and 1.4% for permanent hypoparathyroidism. RESULTS: The 5.8-year survival rate was 92.9%. Fifty-four patients were in Stage I, 35 patients in Stage II, 27 in stage III and 4 in Stage IV. Histological patterns showed the prevalence of papillary type (63.3%) over follicular type (36.7%). CONCLUSIONS: The aggressive surgical approach in well-differentiated thyroid tumours, supported by complementary postoperative therapies, leads to a good control of the disease

Adenocarcinoma, Follicular↗

[Metastases of the thyroid gland--morphology and clinical aspects of 25 secondary thyroid neoplasms].

Morphological and clinical findings in 25 secondary tumours of the thyroid are described. The most common sources of such lesions were the kidneys (32%), lung (28%) and breast (20%). In the majority of cases, thyroidectomy was performed prior to identification and treatment of the primary cancer. Conversely, among renal cell carcinomas, the metastatic lesion frequently appeared many years after resection of the primary tumour. This suggests that secondary thyroid tumours occasionally may be the only important malignant disease remaining. Hence, adequate surgical treatment may prove to be life-prolonging or life-saving.

Aged↗

Pyruvate kinase in normal human thyroid tissue and thyroid neoplasms.

Pyruvate kinase (ATP: pyruvate-2-O-phosphotransferase, EC 2.7.1.40) was studied in human thyroid carcinomas (n = 9), follicular adenomas (n = 32), and normal thyroid tissue (n = 12). The specific activity in carcinomas (mean 0.94 +/- 0.44) is significantly increased (P less than 0.0001) in comparison with pyruvate kinase in normal tissue (mean, 0.14 +/- 0.05). Specific activities of follicular adenomas are rather heterogeneous. When these tumors were divided into three groups of increasing proliferative activity as judged by histopathologic criteria, highest specific activities of pyruvate kinase were found in the group with the highest proliferative activity. On the other hand, specific enzyme activities of the least active tissues (colloid-containing follicular adenomas) were comparable to normal. The isoenzyme composition of normal thyroid tissue is characterized by the presence of K4, K3M, and K2M2 types of pyruvate kinase. In carcinomas, mainly K4 and K3M are found. Undifferentiated tumors express more K4 type compared with follicular and papillary carcinomas. Follicular adenomas with high specific activity show the same electrophoretic pattern as found in follicular carcinomas. Pyruvate kinase from malignant tumors is more inhibited by the amino acid L-alanine than the enzyme from normal thyroid tissue as a consequence of the presence of more K subunits in the malignant tissues. The K4 type from normal thyroid tissue is not kinetically different from the K4 type of carcinomas.

Adenoma↗

Expression of splice variants of CD44 in thyroid neoplasms derived from follicular cells.

Isoform expression of CD44 in follicular carcinoma (FC) of the thyroid was analyzed by immunohistochemical staining and compared to the isoforms in follicular adenoma (FA) and papillary carcinoma (PC) of the thyroid. Variant isoforms of CD44 (CD44v) were detected in these neoplastic cells but not in non-neoplastic cells. CD44v6 was expressed in PC with nodal metastasis and also in FC at significantly higher frequencies than those in PC without metastasis and FA. The frequency of expression of CD44v3 was significantly higher in PC with nodal metastasis than in PC without metastasis. The reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blotting analysis revealed the presence of a transcript for a variant of CD44 that contained variant exon 6 in FA, FC and PC. DNA sequencing of the products of RT-PCR yielded three species of cDNA for CD44v. One of the cDNA corresponded to a transcript that contained variant exon 6. These results suggest that immunohistochemical staining and RT-PCR with Southern blotting analysis for CD44v6 might be a useful diagnostic tool for the differentiation of FC from FA and that the expression of CD44v3 and CD44v6 might be important for the development of nodal metastasis in cases of PC.

Adenoma↗

Quantitative assessment of promoter methylation profiles in thyroid neoplasms.

CONTEXT: Cancer-specific molecular markers are needed to supplement the cytopathological assessment of thyroid tumors, because a majority of patients with cytologically indeterminate nodules currently undergo thyroidectomy without a definitive diagnosis. OBJECTIVE: The aim of this study was the quantitative assessment of promoter hypermethylation and its relation to the BRAF mutation in thyroid tumors. DESIGN: Quantitative hypermethylation of Rassf1A, TSHR, RAR-beta2, DAPK, S100, p16, CDH1, CALCA, TIMP3, TGF-beta, and GSTpi was tested on a cohort of 82 benign and malignant thyroid tumors and five thyroid cancer cell lines. SETTING: The study was conducted at a tertiary research hospital. PATIENTS: Patients underwent surgical resection for a thyroid tumor from 2000 to 2003 at our institution. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURE: Final surgical pathology diagnosis was the main outcome measure. RESULTS: Thyroid tumors showed hypermethylation for the following markers: Rassf1A, TSHR, RAR-beta2, DAPK, CDH1, TIMP3, and TGF-beta. A trend toward multiple hypermethylation was evident in cancer tissues, with hypermethylation of two or more markers detectable in 25% of hyperplasias, 38% of adenomas, 48% of thyroid cancers, and 100% of cell lines. A rank correlation analysis of marker hypermethylation suggests that a subset of these markers is epigenetically modified in concert, which may reflect an organ-specific regulation process. Furthermore, a positive correlation was found between the BRAF mutation and RAR-beta2, and a negative correlation was found between the BRAF mutation and Rassf1A. CONCLUSIONS: Methylation-induced gene silencing appears to affect multiple genes in thyroid tissue and increases with cancer progression. Additional markers with better discriminatory power between benign and malignant samples are needed for the diagnostic assessment of cytologically indeterminate thyroid nodules.

Cell Line, Tumor↗

Induction of thyroid neoplasms in the rat. A histochemical, immunohistochemical, autoradiographic and ultrastructural study.

Papillary carcinomas of the thyroid gland induced in rats by combined methylthiouracil (MTU)/nitrosomethylurea treatment were studied electron microscopically and histochemically for their acid phosphatase activity, radioactive iodine uptake and for their thyroglobulin synthesis. The papillary carcinomas accumulated radioactive iodine, synthesized thyroglobulin and showed a perinuclear localization of acid phosphatase activity in the cytoplasm. After omitting the reactive thyrotropic effect (cessation of MTU administration) a decrease of both iodine organification and acid phosphatase activity was observed. The synthesis of thyroglobulin was also reduced. The changes in the ultrastructure of tumour cells corresponded to the respective functional activities. The results suggest that the papillary carcinomas may have a functional dependence on thyroid-stimulating hormone.

Acid Phosphatase↗

[Malignant thyroid neoplasms at the Geneva Institute of Pathology from 1967-1976].

A survey of all malignant thyroid tumors observed during a ten-year period (1967-1976) in Geneva showed a 8.8% incidence (= 197 cases) of malignancies among surgically removed thyroids and a 0.38% incidence (= 43 cases) at autopsy. In the surgical material, 85% of the tumors were well differentiated carcinomas, while in the post mortem series, only 44% were of the organoid variety, the predominating tumor in this group being the anaplastic carcinoma. These data are comparable to those found in Basel and in Zurich. While the incidence of malignant thyroid tumors seems to remian constant in Switzerland, there is a shift from follicular towards papillary carcinomas within the group of organoid tumors. This change has gradually taken place during the last three to four decades; it has been observed in all three centers and is related, by the author, to the introduction of iodide to kitchen salt in Switzerland.

Autopsy↗

Effect of fine needle aspiration biopsy on the histology of thyroid neoplasms.

We evaluated the effect of fine needle aspiration biopsy (FNAB) upon the histology of thyroid adenoma and differentiated thyroid carcinoma. When surgery was performed within three months of FNAB, infarction was found histologically in 8/82 (9.8%) of the tumors. It was extensive in four patients, with one patient having no residual neoplastic cells identifiable within the nodule. No infarction was seen in the histologic specimens from patients with similar pathology whose surgery was performed without prior FNAB. These findings confirm previous reports that infarction may be caused by FNAB and can be so extensive as to interfere with the histologic diagnosis.

Adenocarcinoma↗

Confocal laser scanning microscopic observation of angioarchitectures in human thyroid neoplasms.

Confocal laser scanning microscopy (CLSM) was employed to study the blood vascular system of human thyroid tumors. CLSM observation combined with immunohistochemistry for type IV collagen clearly visualized 3-dimensional images of the microvascular structures. CLSM observation showed that normal thyroid follicles were tightly covered by branching microvessels, whereas microvessels in follicular adenomas were more prominent and more irregular in shape. Microfollicular adenomas showed that neoplastic small follicles were attached to the capillaries and had a "grape-like" appearance. Strikingly well-developed vascular networks were seen in neoplastic follicles of papillary carcinomas. Interestingly, papillae of papillary carcinoma occasionally contained contained aggregated vascular complexes (glomeruloid structure) composed of tortuous, densely packed, and irregularly arranged small vessels. Such aggregated vascular complexes were seen in 5 of 7 papillary carcinoma tissues but not in other histological thyroid tumors. Our findings indicate that the fundamental vascular pattern correlates well with the growth pattern, suggesting an interdependence between parenchyma and stroma characteristic for thyroid tumors. CLSM observation combined with immunohistochemistry may contribute to a better understanding of morphological characteristics of angioarchitecture in human surgical materials.

Adenoma↗