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PubMed2006

Promising molecular techniques for discriminating among follicular thyroid neoplasms.

To guide the extent of thyroidectomy for indeterminate follicular neoplasm (FN), clinicians have long sought ways to differentiate follicular adenoma from carcinoma pre- or intraoperatively. Several promising molecular techniques have recently appeared including loss of heterozygosity analysis and molecular profiling microarray analysis. These new tools may also prove useful in determining prognosis, thus and allow a paradigm change in current management of the thyroid nodule.

Adenocarcinoma, Follicular↗
PubMed1977

[The unrecognized thyroid neoplasm].

During the last 10 years the authors operated upon 8 patients with illnesses beginning with different lung alterations. In all cases the basic illness was a papillary or papillo-follicular cancer of the thyroid gland which later was found indirectly after other operation and histologic examination. By evaluation of clinical symptoms, operative and morphologic findings conclusions as well as the results of reexamination the authors draw conclusions as to the biological attributes of this tumor type. They recognize that the carcinomas of the thyroid gland cause metastases of regional lymph nodes or distant lung metastases approaching the TO stage. Lung metastases appeared in different shapes and were in all cases the fist clinical sign of the basic illness. Considering the biological attributes of this tumor the authors emphasize that it is not inoperable or untreatable.

Adenocarcinoma↗
PubMed2006

Known pitfalls of the thyroid neoplasm diagnostics in the view of the new (2004) WHO Classification.

The new (2004) WHO Classification of Tumours of the Thyroid and Parathyroid Gland exhibits both formal and contentual changes compared to the previous one from the year 1988. Comparing both texts we have tried to apply the new norm to some recent diagnostic tasks. The classification of poorly differentiated and undifferentiated neoplasms has been successfully solved by employing the immunohistochemical procedures into the daily routine. Nevertheless, some diagnostic problems persist and can not be solved this way. This is true especially for the borderline neoplasm in the FVPTC category and even more for its oncocytic variant. There appeared shift in the criteria for the diagnosis of oncocytic variant of papillary carcinoma. Newly, the obligatory presence of the nuclei with the characteristics of the conventional papillary neoplasms is required. Thorough elaboration of the TNM system has solved the problem of multifocal lesion staging. Moreover, a web consultation source is recommended. The new Classification includes descriptions of the basic cytodiagnostic features. The post aspiration capsular damage consideration in relation to the diagnosis of the minimally invasive follicular carcinoma is one practical profit thereof. In terms of formal logic a criticisable feature of the new classification is the introduction of the so called "Synonyms". These listings include in fact partly real synonyms by definition, but together in one table quite often also subunits or variants of the nosologic units described. In general, the new Classification represents a successful consensus reached. As there are newly also references with varying opinions included, it is presented more like a point of gravity in this field than an undoubted truth. This also makes it a valuable and useful normative text.

Humans↗
PubMed1981

Thyrotropin receptor-adenylate cyclase function in human thyroid neoplasms.

The action of thyrotropin (TSH) on plasma membranes was studied to elucidate the mechanism of hormonal regulation of malignant versus normal human thyroid tissue. Thyroid plasma membranes of six specimens of papillary or follicular carcinoma and six of adenoma, as well as adjacent normal tissue obtained from these patients, were evaluated with respect to binding of 125I-labeled TSH and stimulation of adenylate cyclase. Scatchard analysis of TSH binding revealed the presence of two species of binding sites in normal thyroid of different affinities and capacities. In 11 of 12 tumors studied, the high-affinity binding site remained intact; however, the total number of low-affinity sites was markedly lower than normal tissue. Other parameters of binding were not altered in neoplastic thyroid. In each of these tissues, the hormone responsiveness and kinetics of adenylate cyclase activation were essentially identical to those observed in normal tissue, although basal activity was typically greater in the neoplasm. One carcinoma was totally deficient in both 125I-labeled TSH binding and TSH-stimulatable adenylate cyclase, although basal activity was detected. Furthermore, adenylate cyclase of this specimen was not activated by prostaglandin, in contrast to normal thyroid and other thyroid tumors. These results suggest that: (a) clinical behavior of thyroid carcinomas may not be reflected by TSH receptor-adenylate cyclase function; (b) lack of clinical response as manifest by tumor regression cannot be ascribed to the absence of functional TSH receptors or adenylate cyclase; and (c) decreased low-affinity binding present in tumors is not correlated with altered hormone responsiveness of adenylate cyclase but may reflect more general cancer-induced changes in membrane structure or composition.

Adenoma↗
PubMed1999

[H"urthle cell thyroid neoplasms].

The paper presents up to date knowledge about oncocytic neoplasms (Hürtle cell tumor). The following paper is based on the biggest study group in Poland. Most of these tumors were benign. The histopathological diagnosis was usually very difficult. The authors pointed out that the most important problem in the treatment process was the histopathological examination. Even intraoperative pathological diagnosis is not discriminative for the diagnosis. All diagnoses were based on paraffin-embedded samples examination. In the authors' opinion treatment process should be individualised according to all clinical and histopathological results.

Adenocarcinoma↗
PubMed1998

Sporadic ret-rearranged papillary carcinoma of the thyroid: a subset of slow growing, less aggressive thyroid neoplasms?

Despite the large amount of information accumulated on the role played by ret activation in the oncogenesis of papillary thyroid carcinoma (PTC), the biological and clinical significance of such activation 'in vivo' remains controversial. The aim of this study was to address some of the existing controversies by comparing two groups of unselected PTCs, one with and the other without ret rearrangement, with regard to several clinicopathological and biological features. Thirty-three PTCs were selected at random. ret rearrangement was found in eight cases (24.2 per cent) using Southern blot analysis. The mean age of the patients with tumours displaying ret rearrangement (28 +/- 3.1 years) was significantly lower than that of the patients harbouring cases that did not present rearrangement (45 +/- 2.9 years). The large majority of the tumours with ret rearrangement displayed a papillary or mixed follicular-papillary pattern and very low proliferative activity. ret rearrangement correlated significantly with decreased cytoplasmic expression of E-cadherin. No significant differences were found regarding the gender of the patients, tumour size, multicentricity, extrathyroidal growth, vascular invasion, lymphocytic infiltration, lymph node involvement or the expression of E-cadherin (membrane), c-erb-B2, c-met, Bcl-2, and vimentin. It is proposed that sporadic PTCs harbouring a ret rearrangement occur frequently as slow growing, papillary, or predominantly papillary tumours that do not usually progress towards less differentiated neoplasms representing what might be described as a Bonsai phenotype.

Adolescent↗
PubMedDate not supplied

Multinucleated giant cells in thyroid neoplasms. A cytologic, histologic and immunohistochemical study.

OBJECTIVE: To evaluate the presence of multinucleated foreign body-type giant cells (MGCs) in papillary carcinoma (PC), follicular variant of papillary carcinoma (FV) and follicular adenomas (FA) and to investigate their origin by immunoperoxidase studies. STUDY DESIGN: The cytologic and histologic material of 10 PCs, 8 FVs, and 11 FAs were evaluated for the presence of MGCs. The immunohistochemical staining pattern of MGCs in paraffin-embedded tissue was studied using cytokeratin, epithelial membrane antigen, thyroglobulin, vimentin, A-1 antichymotrypsin, lysozyme and CD68. RESULTS: MGCs were demonstrated in 10/10 PCs, 5/8 FVs and 0/11 FAs. In the immunostained sections, MGCs were negative for epithelial markers and positive for histiocytic markers. CONCLUSION: These results indicate that MGCs are histiocytic and frequently present in PCs and FVs and usually absent from FAs.

Adenoma↗
PubMed1997

Fine-Needle Aspiration in the Evaluation of Thyroid Neoplasms.

Fine-needle aspiration (FNA) is a safe, rapid, and accurate diagnostic tool. Although it continues to gain acceptance, the pace is slow. Probably, if more pathologists master the basics (i.e., learn how to obtain a good sample), this simple technique could be utilized to its fullest advantage. If the sample is not adequate or representative of the lesion, the diagnosis will not be correct. Based on personal experience, we believe that suction should be minimal when obtaining thyroid aspirates. Cytologic diagnostic criteria for the most common neoplasms of the thyroid gland are provided.

Journal Article↗
PubMed1968

Risk of thyroid neoplasms after irradiation in childhood. Studies of populations exposed to radiation in childhood show a dose response over a wide dose range.

The incidence of thyroid carcinoma and of clinically palpable thyroid nodules is compared in three groups of individuals many years after exposure to ionizing radiation in childhood or infancy. The estimated mean cumulative doses to the thyroid gland ranged from 20 rad in the Ann Arbor series irradiated with x-rays as infants for thymic enlargement upward to 1225 rad of mixed radiation (including that from ingested radioiodine) in the Marshallese children. Intermediate between these extremes is the high-risk subgroup in the Rochester series of persons irradiated for thymic enlargement; they received an estimated mean thyroid dose of 335 rad. A plot of the incidence of thyroid nodularity against the total cumulative thyroid dose gives what could be a linear dose response with no threshold or, at least, a threshold below 20 rad. The risk of developing carcinoma in the three studies ranges from 0 to 5.5 cases and that for nodularity 38 to 52 cases per 106 persons exposed per rad (thyroid dose) per year. There is evidence dence from animal experimentation that the biologically effective dose in the case of the Marshallese would have been considerably lower than the cumulative physical dose; hence, the dose response might actually be curvilinear at least in the higher dose range. In view of the uncertainties regarding dose and the assumptions made in my study, the risk values may not be exact; however, these values reflect the trends regarding risks estimated from the best available data in man. Furthermore, the estimated risk values apply only if radiation exposure occurred in childhood.

Child↗
PubMed2005

Expression of N-acetyl transferase human and human Arrest defective 1 proteins in thyroid neoplasms.

Protein acetylation is an important posttranslational modification regulating oncogenesis, apoptosis and cell cycle. NATH (N-acetyl transferase human) is overexpressed at the mRNA level in papillary thyroid carcinomas relative to non-neoplastic thyroid tissue. The NATH protein has recently been demonstrated to be the partner of hARD1 (human Arrest defective 1) and this complex acetylates the N-termini of proteins. ARD1 has also been implicated in the destabilization of the transcription factor HIF-1alpha (hypoxia inducible factor-1alpha). Using human thyroid papillary carcinoma biopsies and NATH- and hARD1-specific antibodies, we examined the levels of endogenous NATH and hARD1 proteins in 27 patients. We demonstrate that NATH protein level is upregulated in neoplastic versus non-neoplastic tissue in good accordance with our previous mRNA findings. In all tumors in which NATH was downregulated compared to non-neoplastic tissue, the hARD1 protein level was concomitantly reduced. SiRNA-mediated knockdown of NATH resulted in decreased levels of hARD1 protein. Taken together, these results suggest that NATH positively affects the level of hARD1 protein both in vivo and in cell cultures.

Acetyltransferases↗
PubMed2004

Complication of thyroidectomy in patients with radiation-induced thyroid neoplasms.

HYPOTHESIS: The complication rate for thyroidectomy is the same in patients with and without a history of radiation exposure. DESIGN: Retrospective medical record review of 171 consecutive patients who had a previous history of radiation treatment and had undergone a thyroid operation from 1961 to 1999. SETTING: University of California, San Francisco, Medical Center and affiliated hospitals. PATIENTS: We selected 107 patients with a history of radiation exposure who had undergone thyroid operations (81 total thyroidectomies) and 107 control patients who underwent comparable operations but had no history of radiation exposure. RESULTS: Among patients with a history of radiation exposure (mean age, 47.2 years), there was 1 recurrent nerve injury, 1 external nerve injury, 20 patients with transient hypocalcemia, and 1 patient with a hematoma. Among patients without a history of radiation exposure (mean age, 47.5 years), there were 2 recurrent nerve injuries, 18 patients with transient hypocalcemia, and 1 patient with a hematoma. All cases of hypocalcemia and recurrent nerve injury in both groups were transient. One patient had a permanent superior laryngeal nerve injury. In patients who underwent operations since January 1, 1990, duration of hospitalization was 1.2 days in patients with a history of radiation exposure (65 patients) and 1.1 days in patients without (101 patients). CONCLUSIONS: Our data document that the risk of transient and permanent complications after total thyroidectomy is similar in patients with and without a history of radiation exposure. The relatively low long-term complication rate supports prophylactic total thyroidectomy for patients with thyroid nodules and a history of radiation exposure.

Female↗
PubMed1991

Immunoscintigraphic localization in a benign thyroid neoplasm of a monoclonal antibody directed against melanoma.

In a prospective study for evaluation of the use of a monoclonal antibody directed against melanoma in the staging of patients affected by malignant melanoma, we report monoclonal antibody uptake in a follicular thyroid adenoma. Computed tomography, ultrasonography, and pertechnetate scintigraphy did not provide a certain diagnosis. Only pathologic examination of the surgical specimen was conclusive.

Adenoma↗
PubMed2006

High-level expression, activation, and subcellular localization of p38-MAP kinase in thyroid neoplasms.

The p38 family of MAP kinases (p38-MAPKs) is involved in regulating the proliferation, survival, and migration of various cancer cells. The present study has investigated the expression, subcellular localization, phosphorylation, and activity of p38-MAPKs in normal and tumoural human thyroid tissues and in thyroid cell lines. The expression and nucleo-cytosolic compartmentalization of the alpha-isoform of p38-MAPKs (p38alpha-MAPK) were studied by western blotting in the WRO and B-CPAP cell lines, which are derived from human follicular and papillary thyroid carcinomas, respectively, and in the non-transformed rat thyroid cell lines FRTL-5 and PCCL3. Immunohistochemistry was used to study the expression and subcellular localization of p38alpha-MAPK, and of the phosphorylated forms of p38-MAPKs (P-p38-MAPKs) in human toxic adenomas (TAs), follicular adenomas (FAs), papillary thyroid carcinomas (PTCs), and follicular thyroid carcinomas (FTCs). The activity of p38-MAPKs in PTCs and FTCs was revealed by immunohistochemical detection of their typical phosphorylated substrate, MAPK-activated protein kinase 2/3 (MK2/3). p38alpha-MAPK was expressed in all cell lines and this expression was restricted to the cytosolic compartment. p38 MAPK activity was involved in regulating DNA synthesis in B-CPAP cells. p38alpha-MAPK and P-p38-MAPKs were strongly expressed in PTC and FTC cells, although only in the cytoplasm, whereas they were only very weakly expressed in FA cells, and absent in adjacent normal tissues. They were also expressed at a high level in TAs, but they were found in both nucleus and cytoplasm. Finally, phospho-MK2/3 immunostaining followed very similar patterns to those of p38alpha-MAPK and P-p38-MAPKs in PTCs and FTCs. Taken together, these results show for the first time that the p38-MAPK signalling cascade is functional in two types of differentiated carcinoma of the thyroid. The observation that p38-MAPK hyper-expression occurs in FTC, but not in FA, may provide an additional diagnostic tool for malignancy in some thyroid nodules.

Adenocarcinoma, Follicular↗
PubMed1975

99mTc-pertechnetate thyroid scintigraphy in patients predisposed to thyroid neoplasms by prior radiotherapy to the head and neck.

Histories, physical examinations and 99mTc-pertechnetate imaging were used to evaluate 1,452 persons who had had x-ray therapy to the neck region for benign conditions 18 to 35 years previously. Thyroid abnormalities were found in 301 patients (21%) and thyroid malignancy was found in 29% of 193 patients with abnormal studies who were explored surgically. Thyroid imaging detected 96% of these abnormalities, 40% of which would not have been unequivocally established by physical examination alone. Nuclear imaging could not distinguish benign from malignant lesions.

Adenocarcinoma↗
PubMed2001

Clinical relevance of vascular endothelial growth factor for thyroid neoplasms.

Angiogenesis is of vital importance during the development and progression of solid tumors. Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis and could be produced by some cancer cells. To investigate the clinical relevance of VEGF in the tumorigenesis of human thyroid, an immunohistochemical study was performed on archival materials of follicular adenomas (n = 13), Hürthle cell adenomas (n = 6), papillary carcinomas (n = 76), follicular carcinomas (n = 12), Hürthle cell carcinomas (n = 2), and anaplastic carcinomas (n = 8). Patterns of VEGF expression were analyzed in relation to histologic subtypes of thyroid tumors and were correlated to biologic indicators of papillary carcinoma. All papillary carcinomas and Hürthle cell neoplasms revealed a strong, diffuse staining reaction, whereas anaplastic carcinoma usually exhibited weak and infrequent immunoreactivity. VEGF levels were usually higher in follicular adenomas than in follicular carcinomas. With regard to prognostic value, VEGF expression did not correlate with tumor size, extent of invasion, or scores on the AGES system (i.e., patient age, tumor size, histologic grade, tumor extent, distant metastasis) or the MACIS system (i.e., metastasis, age, completeness of resection, invasion, tumor size) for papillary carcinomas (p > 0.05, respectively). The results of the current study indicate that VEGF may play a role in the development of human thyroid cancer. Determination of the angiogenic phenotype may have limited prognostic value for patients with papillary carcinoma.

Adenoma↗
PubMed2004

A reanalysis of thyroid neoplasms in the Israeli tinea capitis study accounting for dose uncertainties.

In the 1940s and 1950s, children in Israel were treated for tinea capitis by irradiation to the scalp to induce epilation. Follow-up studies of these patients and of other radiation- exposed populations show an increased risk of malignant and benign thyroid tumors. Those analyses, however, assume that thyroid dose for individuals is estimated precisely without error. Failure to account for uncertainties in dosimetry may affect standard errors and bias dose-response estimates. For the Israeli tinea capitis study, we discuss sources of uncertainties and adjust dosimetry for uncertainties in the prediction of true dose from X-ray treatment parameters. We also account for missing ages at exposure for patients with multiple X-ray treatments, since only ages at first treatment are known, and for missing data on treatment center, which investigators use to define exposure. Our reanalysis of the dose response for thyroid cancer and benign thyroid tumors indicates that uncertainties in dosimetry have minimal effects on dose-response estimation and for inference on the modifying effects of age at first exposure, time since exposure, and other factors. Since the components of the dose uncertainties we describe are likely to be present in other epidemiological studies of patients treated with radiation, our analysis may provide a model for considering the potential role of these uncertainties.

Adolescent↗
PubMedDate not supplied

The surgical management of benign and malignant thyroid neoplasms in Marshall Islanders exposed to hydrogen bomb fallout.

On March 1, 1954, a serious fallout accident occurred during the United States atomic testing program at Bikini in the Trust Territory of the Pacific Islands. Following the detonation of a large thermonuclear device (known as Bravo) an unexpected shift in winds resulted in deposition of radioactive debris on several inhabited atolls in the Marshall Islands. During the early post-detonation period military, sea, and air surveys traced the hottest portion of the parabolic cloud as it drifted in an ever widening pattern of diminishing concentration eastward and southeast of Bikini. The center of the cloud passed North of the Rongelap Atoll, which was the nearest inhabited atoll. This report concerns the development of thyroid lesions, the special circumstances encountered during thyroid surgery, and the results of the surgical management of benign and malignant lesions that were subsequently encountered in this population.

Adenoma↗