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PubMed2005

Cervical chordoma masquerading as a thyroid neoplasm: a case report.

Chordomas are rare neoplasms of notochord derivation that arise along the craniospinal axis. Their incidence along the cervical spine and close proximity to the thyroid can pose diagnostic pitfalls. We report a case of a paraspinal mass juxtaposed adjacent to the thyroid with intranuclear inclusions of papillary carcinoma, abundant eosinophilic cytoplasm of an oncocytic lesion, and pleomorphism of anaplastic carcinoma that expressed thyroglobulin and emulated a malignant thyroid neoplasm. However, subsequent histological examination revealed a chordoma with perithyroidal soft-tissue invasion. This case highlights the significance of including chordoma in the differential diagnosis of a thyroid neoplasm and interpreting thyroglobulin reactivity warily, because its inadvertent tracking during fine-needle aspirates (FNAs) can produce false positive staining of nonthyroidal cells.

Aged↗
PubMed1995

The natural protein kinase C alpha mutant is present in human thyroid neoplasms.

An altered protein expression of Ca(2+)-dependent protein kinase C (PKC) isoforms and a point mutation in the PKC alpha cDNA (position 908 of the nucleotide sequence, position 294 of the amino acid sequence, substitution of an aspartic acid by a glycine) have been previously described in a subpopulation of human pituitary tumors. In this work, we screened 16 thyroid tissue samples (four follicular adenomas, five colloid adenomas, three papillary carcinomas, one follicular carcinoma and three normal tissues adjacent to the tumors) for the presence of the PKC alpha point mutation and for PKC alpha, beta 1, beta 2, epsilon and delta protein expression. Screening for the presence of the PKC alpha mutant was performed by a subcloning technic. The polymerase chain reaction products were generated using reverse-transcribed cDNAs, subcloned and sequenced (10 clones were routinely sequenced). The PKC alpha point mutation at position 908 of the cDNA sequence was found in four out of the nine adenomas and in the follicular carcinoma. It was neither detected in the papillary carcinomas nor in the adjacent normal tissues (one was the adjacent normal tissue of the follicular carcinoma; in this sample, genomic DNA and cDNA were used to look for the presence of the mutant), demonstrating the somatic nature of this mutant. Western blot analysis of PKC isoforms showed that the expression of all isoforms was higher in the thyroid neoplasms as compared with their adjacent normal tissue (n = 3). It was also higher in the samples containing the PKC mutant (two follicular adenomas, two colloid adenomas and the follicular carcinoma) as compared with the tumors where it was not detected (three papillary carcinomas and five adenomas). Samples could be ordered according to their increasing PKC expression as follows: normal adjacent tissue < follicular adenomas without PKC alpha mutant < or = papillary carcinoma < follicular adenomas with PKC mutant < follicular carcinoma with PKC mutant. In conclusion, the discovery of the PKC alpha mutant in thyroid neoplasms demonstrates that this mutant is not particular to human pituitary tumors where it was originally detected. It is a somatic mutation and its presence is concomitant with high levels of all of the PKC isoforms analysed. The presence of the PKC mutant in thyroid neoplasms raises the question of its importance in thyroid tumorigenesis.

Adenocarcinoma, Follicular↗
PubMedDate not supplied

Bag-1 expression in thyroid neoplasm: its correlation with Bcl-2 expression and carcinoma dedifferentiation.

BACKGROUND: Apoptosis, programmed cell death, is one of the promnent factors in the evaluation of carcinoma characteristics. It is well-known that bcl-2 and its related proteins significantly modulate apoptosis. Bag-1 is a recently identified bcl-2-related protein and is known to be linked to the biological aggressiveness of some carcinomas. MATERIALS AND METHODS: We immunohistochemically investigated bag-1 and bcl-2 expression in various thyroid neoplasms using monoclonal antibodies. RESULTS: High bag-1 expression was observed in 66.7% of follicular adenoma and 75.0% of follicular carcinoma, and no statistical difference was established between them. In papillary carcinoma, 60.7% were classified with high bag-1 expression, whereas only 4.5% of anaplastic (undifferentiated) carcinoma highly expressed bag-1, and the incidence was significantly lower (p < 0.0001) than in papillary and follicular carcinomas. Furthermore, in thyroid neoplasm, bag-1 expression was directly linked (p < 0.0001) to bcl-2 expression. CONCLUSION: These findings suggest that bag-1 may interact with bcl-2 to play an important role in thyroid neoplasm before anaplastic transformation, and the disruption of events mediated by bag-1 and bcl-2 may be a typical characteristic of undifferentiated carcinoma.

Adenocarcinoma, Follicular↗
PubMed1980

Unilateral thyroid neoplasm in a cat.

An aged cat with a thyroid neoplasm showed clinical signs and had laboratory data and post mortem findings similar to those observed in human and canine patients afflicted with hyperthyroidism. Because of these similarities hyperthyroidism was suspected in the cat.

Adenoma↗
PubMed1994

[Teleradiotherapy in the treatment of thyroid neoplasms].

The role of external radiotherapy in the treatment of thyroid neoplasms is not yet well defined. The indications for loco-regional treatment in the case of: anaplastic carcinomas (alone or in combination with surgery or chemotherapy); differentiated and medullary carcinomas at diagnosis or relapse; nodes or osseous metastases not otherwise curable (surgery, hormones, brachytherapy); cerebral metastases; are accepted by everyone. Results, from the various clinical reports published, are positive. The use of this methodology is not accepted by everyone as "adjuvant" in cases "at risk" for micro or macroscopic residuals after surgery for papillary, follicular or medullary carcinomas. From the analysis of the literature, even a recent publication in relation to an apparent growing local control, we have no data in favour of increased survival. Even from our experience we cannot give definitive data (78.5% of local control in case of papillary or follicular carcinoma, survival of 57% in 5 years and 36% in 10 years). The question could be solved only by randomised trials but the difficulties due to the need for a sufficient number of cases and to the long "natural" survival, even in presence of disease, appear to be insuperable. We suggest a prudent approach, in controversial cases, because of the difficulties linked to the optimal loco-regional treatment (high doses, proximity of organs "at risk").

Adenocarcinoma, Follicular↗
PubMed1998

Apoptosis in thyroid neoplasms: relationship with p53 and bcl-2 expression.

AIM: Cell gain and loss occurs concurrently in tumours. Apoptosis may play a major role in determining the growth and aggressiveness of the tumours. The aim of this study was to investigate whether apoptosis is related to the degree of differentiation and expression of mutated p53 and bcl-2 in thyroid neoplasms. METHODS AND RESULTS: Fifty-three thyroid tumours of various histological types and 10 multinodular goitres were investigated semiquantitatively for the presence of apoptosis using a DNA end ligase method. Simultaneously, quantitative immunostaining was performed for bcl-2 and p53, two known regulators of apoptosis. No apoptosis was detected in normal thyroid tissues, multinodular goitres and in four follicular adenomas, all of which were positive for bcl-2. On the other hand, two anaplastic and one insular carcinomas showed marked increase in apoptosis along with intense p53 positivity and bcl-2 negativity. The majority of the follicular carcinomas showed results similar to that of follicular adenomas. No apoptosis was detected in 41% of papillary carcinomas, the majority of these being p53 negative and bcl-2 positive. Forty-four per cent of the papillary carcinomas demonstrated low apoptosis rate, with variable bcl-2 positivity and mostly negative for p53. Fifteen per cent of papillary carcinomas showed a high apoptosis rate. They were p53 negative and mostly negative for bcl-2. The differences of staining in various tumours with respect to p53, bcl-2 and apoptosis were statistically significant. Correlation analysis demonstrated a significant relationship between apoptosis and bcl-2 expression in thyroid tumours (P < 0.001), whereas no relationship was seen with p53. CONCLUSION: These data suggest that bcl-2 expression in thyroid neoplasms is related to apoptosis, p53 expression is associated with high grade thyroid tumours, but may not be important in the apoptotic pathways in all thyroid tumours.

Apoptosis↗
PubMed1990

The measurement of DNA content and ploidy analysis in thyroid neoplasms.

It is clear that the DNA content of endocrine cells is influenced by factors other than neoplastic change and transformation. Although it can be concluded that, in general, the DNA content of neoplasms is increased, it is less clear whether this increase in DNA content is the cause or the effect of neoplastic transformation. The actual consequences of an increased DNA content are still largely unknown. However, based on a substantial body of data on the measure of nuclear DNA content in thyroid neoplasms, several conclusions appear to be reasonable. First, the measurement of nuclear DNA content and ploidy analysis are not sufficiently reliable parameters upon which to distinguish a benign from a malignant thyroid neoplasm. Therefore, this parameter has failed to live up to the expectation that it would be a powerful diagnostic tool. Second, the measurement of nuclear DNA content is useful after a histomorphologic diagnosis has been made since it correlates very well with the prognosis and clinical outcome of the patient. It is clear that aneuploid thyroid carcinomas are responsible for earlier recurrence, an increased likelihood of distant and diffuse metastases, and an increased incidence of death compared with diploid thyroid carcinomas. Except for the rare occasion, diploidy implies a uniformly long-term survival whereas aneuploidy is associated with a variable clinical course. Irrespective of histomorphology, lethal lesions of the thyroid are invariably aneuploid, whereas lesions associated with prolonged survival or a favorable outcome can be either diploid or aneuploid. Aneuploidy in well-differentiated thyroid carcinoma is more likely in older patients, in less well-differentiated neoplasms, and in neoplasms infiltrating beyond the thyroid capsule. Age, type of neoplasm, extrathyroidal extension, and recurrent disease all appear to be more important prognostic variables than is nuclear DNA content. However, nuclear DNA content can increase the prognostic power of these variables and consequently may come to be increasingly useful in the management of some patients with thyroid neoplasms. After a histomorphologic diagnosis has been made, the measurement of nuclear DNA content and a determination of the DNA ploidy may have significant prognostic value.

DNA, Neoplasm↗
PubMed1994

Expression of thyroid-specific transcription factors TTF-1 and PAX-8 in human thyroid neoplasms.

TTF-1 and PAX-8 are tissue-specific transcription factors expressed in the thyroid follicular cells, contributing to the maintenance of the differentiated phenotype. In fact, it has been demonstrated that TTF-1 and PAX-8 are able to activate transcription from thyroglobulin and thyroperoxidase (TPO) promoters, the transcriptional activity of which is in vivo restricted only to the thyroid follicular cell. In order to gain insight into how these transcription factors control in vivo the differentiation of the thyroid cell and to have a better molecular characterization of human thyroid tumors, TTF-1, PAX-8, thyroglobulin, and TPO mRNA levels were measured in nonmalignant and malignant human thyroid tissues. Results indicate that the expression of TTF-1 and PAX-8 is not sufficient per se for the expression of the thyroid-differentiated phenotype. Furthermore, in follicular adenomas, PAX-8 mRNA levels are strictly related to TPO mRNA levels, suggesting that the amount of PAX-8 could play a role in the modulation of TPO gene expression. TTF-1 mRNA is always well detectable in papillary carcinomas and, in contrast, always absent in anaplastic carcinomas. Identical results were obtained when the expression of TTF-1 protein was investigated using immunohistochemistry. Thus, TTF-1 gene expression could be a molecular marker in order to distinguish these two types of thyroid neoplasms.

Adenocarcinoma, Follicular↗
PubMed1995

Histochemical demonstration of different types of poly-N-acetyllactosamine structures in human thyroid neoplasms using lectins and endo-beta-galactosidase digestion.

Blood-group-related antigens expressed in papillary carcinomas and other types of neoplasm of the human thyroid glands have been shown to be carried by poly-N-acetyllactosamines containing a linear domain susceptible to endo-beta-galactosidase digestion. To make clear more precisely the backbone poly-N-acetyllactosamine structures, labelled lectins specific to different types of these structures and specific to core structures with beta 1-6GlcNAc branching of N- and O-linked glycoproteins were employed in conjunction with prior endo-beta-galactosidase digestion on formalin-fixed, paraffin-embedded neoplasms of the human thyroid glands. In papillary carcinomas, Datura stramonium agglutinin (DSA) and succinyl wheat germ agglutinin (Suc-WGA) reacted most consistently and frequently with papillary carcinomas from all the individuals examined. Pokeweed mitogen (PWM) likewise stained the cells of papillary carcinomas from all the individuals examined, but in some individuals the number of lectin-reactive cells were very small. Lycoperscion esculentum aggultinin (LEA), Solanum tuberosum agglutinin (STA), Phaseolus vulgaris agglutinin L (PHA-L) and Artocarpus integrifolia agglutinin (jacalin) similarly bound to the cancer cells from most of the individuals, and in these cases the number of reactive cells was usually much more restricted than was the case with DSA or PWM. In adenoma and other types of carcinoma, such as follicular carcinomas, these lectins specific to poly-N-acetyllactosamine exhibited slight or no reactivity with the cells, whereas PHA-L and jacalin similarly bound to the cells of adenomas and carcinomas from most of the individuals examined. Prior digestion with endo-beta-galactosidase completely eliminated or markedly reduced the reactivity with PWM and LEA in papillary carcinomas. Reactivity with DSA, Suc-WGA, STA, PHA-L and jacalin was slightly reduced or not at all affected by enzyme digestion. These results confirmed that poly-N-acetyllactosamine species found in papillary carcinomas are quite different from those in other types of thyroid neoplasm, suggesting that at least three different types of poly-N-acetyllactosamine, that is, linear unbranched short and long sequences and highly branched ones are produced in these cells.

Adult↗
PubMedDate not supplied

Histology and fine-needle aspiration cytology of malignant thyroid neoplasms.

Malignant neoplasms of the thyroid are relatively infrequent tumors which present, like most pathological processes of this gland, as nodules. The commonest types are carcinomas, divided into papillary, follicular, medullary, insular and anaplastic carcinoma. Much less frequent are lymphomas and other non-epithelial malignancies. The fine-needle aspiration biopsy (F.N.A.B.) is the first choice method to investigate nodular thyroid lesions and to detect malignant tumors.

Biopsy, Needle↗
PubMed2004

Gene expression profiling of differentiated thyroid neoplasms: diagnostic and clinical implications.

PURPOSE: The purpose of this research was to identify novel genes that can be targeted as diagnostic and clinical markers of differentiated thyroid tumors. EXPERIMENTAL DESIGN: Gene expression analysis using microarray platform was performed on 6 pathologically normal thyroid samples and 12 primary follicular and papillary thyroid neoplasms. Microarrays containing probes for 5,760 human full-length cDNAs were used for hybridization with total RNA from normal and tumor thyroid samples labeled with Cy3-dUTP and Cy5-dUTP, respectively. Scanned array images were recorded, and data analysis was performed. Selected sets of differentially expressed genes were analyzed using quantitative real-time reverse transcription-PCR for verification. RESULTS: We identified 155 genes that differentiate histologically normal thyroid tissues from benign and malignant thyroid neoplasms. Of these 75 genes were differentiated between follicular neoplasms (adenoma and carcinoma) and the follicular variant of papillary carcinoma. Purely follicular neoplasms (adenomas and carcinomas) shared many genetic profiles, and only 43 genes were distinctly different between these tumors. Hierarchical cluster analysis also differentiated conventional papillary carcinoma from its follicular variant and follicular tumors. The differentially expressed genes were composed of members of cell differentiation, adhesion, immune response, and proliferation associated pathways. Quantitative real-time reverse transcription-PCR analysis of selected genes corroborated the microarray expression results. CONCLUSIONS: Our study show the following: (1) differences in gene expression between tumor and nontumor bearing normal thyroid tissue can be identified, (2) a set of genes differentiate follicular neoplasm from follicular variant of papillary carcinoma, (3) follicular adenoma and carcinoma share many of the differentiated genes, and (4) gene expression differences identify conventional papillary carcinoma from the follicular variant.

Adenocarcinoma, Follicular↗
PubMed1985

Thyrotropin regulation of adenylate cyclase activity in human thyroid neoplasms.

Thyrotropin (TSH), stimulators of guanyl nucleotide regulatory protein, (sodium fluoride and guanyl-5'-yl-imido-diphosphate [Gpp(NH)p]) and a stimulator of the catalytic unit of adenylate cyclase (AC) (forskolin) were used to probe the TSH receptor-guanyl nucleotide regulatory protein-cyclase unit in normal and neoplastic thyroid tissue from 17 patients. Eleven of these patients had benign follicular adenomas and six patients had differentiated thyroid carcinomas. An 8000 X g particulate fraction that is rich in thyroid plasma membranes was prepared, and the activity of AC was determined by the conversion of alpha-32P-ATP to P32-cAMP. Thyroid neoplasms had a greater AC response to TSH than did normal thyroid tissue removed from the same patients (p less than 0.001). The AC response to NaF and Gpp(NH)p was greater in the neoplastic thyroid tissue, although in these experiments the increase was not significant. In contrast, the AC response to forskolin was comparable in normal (573 +/- 129) and neoplastic (526 +/- 132) thyroid tissue (mean +/- SEM). The effects of NaF, Gpp(NH)p, and forskolin on AC activity were additive with TSH when used at concentrations for optimal AC activity. Low concentrations of NaF and Gpp(NH)p stimulated AC activity whereas high concentrations of NaF and Gpp(NH)p assayed either together or separately inhibited AC activity. When forskolin and NaF were assayed together there was a greater than additive effect or potentiated effect on activity. Basal AC activity was increased in the presence of manganese (Mn+2) (2 mM) over magnesium (Mg+2) (2 mM) (p less than 0.001), whereas TSH-stimulated (p less than 0.01) and Gpp(NH)p-stimulated AC activity (p less than 0.05) were lower in the presence of Mn+2 than Mg+2. There was an excellent correlation between basal AC activity and AC activity in response to forskolin in both normal and neoplastic thyroid tissue, whereas there was no correlation between basal AC activity and TSH-stimulated AC activity in the thyroid neoplasms. These data suggest that the abnormality responsible for the greater AC response to TSH in neoplastic thyroid tissue is proximal to the catalytic unit of AC and most probably is due to an alteration in the guanyl nucleotide regulatory protein or in the coupling of the guanyl nucleotide regulatory protein to either the receptor or the catalytic unit of AC.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoma↗
PubMed1996

Two-dimensional proton magnetic resonance spectroscopy for tissue characterization of thyroid neoplasms.

We have previously demonstrated that one dimensional (1D) proton (1H) magnetic resonance spectroscopy (MRS) can distinguish normal thyroid tissue from thyroid carcinoma using a spectral ratio of peak intensity at 1.7 ppm/0.9 ppm. Two dimensional (2D) 1H-MRS allows identification of specific molecules that have overlapping peaks in the 1D-MR spectrum. Specimens from 93 consecutive thyroid nodules were examined using 2D 1H-MRS on a Bruker AM-360 wide-bore spectrometer. There was a progressive increase in lipid cross peaks assigned to di-/triglycerides when comparing colloid/hyperplastic nodules to follicular adenoma, and adenoma to carcinoma. A specific cross peak attributable to cholesterol/cholesteryl esters was commonly seen in carcinomas. In contrast, two unassigned cross peaks unique to the thyroid were more prevalent in benign lesions. There was an overall increase in cross peaks attributable to cell surface fucosylation in carcinoma when compared to benign lesions, although the fucose spectral pattern was not specific for cancer. On this basis, a spectral ratio of peak intensity at 2.05 ppm/0.9 ppm more clearly distinguished benign follicular adenoma from carcinoma. 2D 1H-MRS thus identifies chemical changes that allow more specific tissue characterization of thyroid neoplasms.

Adenoma↗
PubMed2003

Y-box binding protein expression in thyroid neoplasms: its linkage with anaplastic transformation.

Recent studies have demonstrated that Y-box binding protein (YB-1) regulates the transcription of genes linked to carcinoma progression. In this study, we investigated the expression of this protein in thyroid neoplasms to elucidate its significance. The expression of YB-1 was immunohistochemically investigated using the monoclonal antibody for various thyroid neoplasms. Normal follicles did not overexpress YB-1, and only moderate overexpression of YB-1 was observed in some follicular tumors and papillary carcinoma, especially those of a larger size. In contrast, 92.9% of anaplastic carcinoma strongly overexpressed YB-1. YB-1 immunoreactivity was seen in both cytoplasms and cell nuclei, but the former was more predominant. These findings suggest that YB-1 plays a role in regulating the transcription as well as translation of genes contributing to the anaplastic transformation of thyroid carcinoma.

Adenocarcinoma, Follicular↗
PubMed1999

Expression of vascular endothelial growth factor (VEGF) in human thyroid neoplasms.

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is an angiogenic factor that plays important roles in tumor growth. Angiogenesis studies on VEGF deal with various types of malignant tumors, but very little is known about the role or significance of VEGF in human thyroid neoplasms. Therefore, in the current study, we determined whether VEGF is found in normal and neoplastic thyroids and whether its expression is altered in different histological types of thyroid neoplasms. Reverse-transcription polymerase chain reaction (RT-PCR) analysis showed that all specimens of thyroid tumors expressed bands corresponding to 121-, 165-, and 189-amino acid forms of VEGF. Northern blot analysis showed an increase in VEGF mRNA levels in neoplastic tissues in comparison with normal thyroid samples. By nonisotopic in situ hybridization, most of the tumor cells in follicular adenomas expressed VEGF mRNA, whereas VEGF mRNA expression was identified only in epithelium of isolated follicles in normal thyroid tissues. In papillary thyroid carcinomas, an intense labeling with VEGF probe was often found in overlying tumor cells of neoplastic papillae. VEGF expression was distinctly intensified in undifferentiated carcinoma cells that were immediately adjacent to necrotic foci. The immunohistochemical localizations of VEGF protein were comparable to the localization of VEGF mRNA. In conclusion, our results suggest that the histological types of thyroid tumor may determine the vascular pattern through a paracrine mechanism involving VEGF.

Blotting, Northern↗