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[Follicular thyroid tumor as a diagnostic and therapeutic problem].

Although the appearance of follicular thyroid tumors in the population is high, only a small part of them are malignant. Follicular tumors are built of follicular epithelial cells and are encapsulated. Cell atypia differentiates follicular adenoma from cancer. Follicular cancer is characterized by vascular invasion and causes metastases through blood vessels, mainly to lungs and bones. In the diagnosis of follicular thyroid neoplasm, pathological examination of postoperative material plays a leading role. In diagnosis before surgical treatment, physical examination, ultrasound (USG), and fine needle aspiration biopsy (FNAB) are of great importance. The choice of treatment in patients in which follicular neoplasm has been diagnosed by FNAB awakes controversies. In practice it is impossible to determine reliably before surgery whether the lesion is malignant or not. Because of the rare incidence of thyroid cancer in the general population, more and more authors tend to decide on partial resection of the thyroid gland and possible radicalization if cancer is diagnosed on paraffin specimen examination.

Adenocarcinoma, Follicular↗

Angiomatoid carcinoma of the thyroid gland. Anaplastic carcinoma with follicular and medullary features mimicking angiosarcoma.

A 79-year-old man with a 28-year history of a substernal goiter had an anaplastic thyroid neoplasm with prominent angiomatoid features develop. Based on the light microscopic appearance of the tumor and the presence of immunocytochemical staining for Factor VIII-related antigen, a diagnosis of angiosarcoma was made. Subsequent immunocytochemical and ultrastructural studies suggested follicular and medullary differentiation without staining for Ulex europeaus I lectin or evidence of Weibel-Palade bodies. Based on these findings, the tumor is interpreted as an anaplastic carcinoma with evidence of mixed follicular and medullary differentiation and extensive intravascular growth producing an angiomatoid appearance. Positivity for Factor VII-related antigen may be due to nonspecific uptake of antigen-rich serum and platelets by the phagocytic tumor cells. Factor VIII-related antigen immunoreactivity should be interpreted with caution in intravascular neoplasms.

Adenocarcinoma↗

Thyroid carcinoma and hyperthyroidism in a dog.

A 10-year old spayed, female Labrador retriever, with an 8-month history of weight loss, increased heart rate, and hyperactivity, was diagnosed with hyperthyroidism and a thyroid neoplasm. Thyrotoxic heart disease is documented in this case.

Animals↗

[Osteosarcoma of the thyroid gland (author's transl)].

A case of an osteogenic sarcoma of the thyroid gland is reported. From the cases described in the literature the most important points of interest of these rare thyroid neoplasms are summarized and the histological differentialdiagnostic criteria to anaplastic carcinoma are discussed.

Aged↗

Venous involvement by follicular carcinoma of the thyroid gland.

Involvement of the great veins by thyroid neoplasms is a rare event: to date 9 cases have been reported and only 2 of them have been surgically treated. The authors describe a case of follicular thyroid carcinoma involving the proximal tract of the left innominate vein at its confluence with the superior vena cava: a neoplastic bud was protruding into the lumen, but the endothelial lining appeared to be perfectly preserved. Full radicality was obtained by a major vascular procedure.

Adenocarcinoma↗

Anaplastic thyroid cancer evolved from papillary carcinoma: demonstration of anaplastic transformation by means of the inter-simple sequence repeat polymerase chain reaction.

BACKGROUND: In thyroid tumors, the coexistence of well- and poorly differentiated tumor types has led to the hypothesis that poorly differentiated thyroid tumors develop from well-differentiated thyroid tumors. By evaluating the genomic instability of histologically distinct but coexisting tumor foci, this study aimed to develop an improved understanding of thyroid tumorigenesis and tumor evolution. DESIGN: Laser capture microdissection (LCM) was carried out on archival formalin-fixed, paraffin-embedded sections from a tumor containing foci of classic papillary thyroid cancer and anaplastic thyroid cancer. DNA was extracted from each microdissected tumor focus. In addition, cryopreserved bulk normal and neoplastic thyroid tissue underwent DNA extraction. All DNA samples were subsequently evaluated for genomic instability by means of inter-simple sequence repeat polymerase chain reaction. RESULTS: The LCM DNA from each archival paraffin-embedded tumor focus demonstrated unique patterns of banding as compared with the cryopreserved tumor and normal tissue DNA. Thus, intratumoral variability in genomic instability was observed. Comparison of inter-simple sequence repeat polymerase chain reaction patterns of LCM DNA from adjacent foci of papillary and anaplastic tumors showed conserved genome alterations. CONCLUSIONS: At the genome level, thyroid tumors may be highly heterogeneous. The intratumoral histologic heterogeneity observed in thyroid neoplasms reflects genetically heterogeneous underlying tumor cell populations that are demonstrated by the observed differences in their rates and extents of genomic instability. The conserved genomic alterations in the microdissected papillary and anaplastic foci suggest intratumoral evolution, with transformation of a preexisting papillary tumor to anaplastic carcinoma.

Aged↗

Fat-containing lesions of the thyroid gland.

Thyroid lesions containing adipose tissue are rare; only scattered case reports are recorded. This study of 17 lipomatous thyroid lesions on file at the Armed Forces Institute of Pathology was undertaken to better document the full range of these abnormalities. Patient ages ranged from 11 to 75 years; nine patients were female and eight were male. Fat-containing thyroid neoplasms included seven papillary carcinomas, four adenomatoid nodules, one follicular adenoma, and one minimally invasive follicular carcinoma. Nonneoplastic conditions associated with adipose tissue included four cases of amyloid goiter, two cases of lymphocytic thyroiditis, one case of dyshormonogenetic goiter, and one case of thyroid atrophy. This study documents the presence of adipose tissue in a wider range of benign and malignant thyroid lesions than has previously been reported.

Adipose Tissue↗

[Use of tumor markers in monitoring thyroid carcinoma].

The authors report on their experience regarding the use of tumours markers for the pre-operative monitoring and subsequent follow-up of patients suffering from thyroid carcinoma. All patients were subjected to radio-immuno-assay for circulating thyroglobulin, a valuable indicator of residual and metastatic thyroid tissue. The patients suffering from medullary carcinoma of the thyroid and their immediate families were also monitored by periodic thyrocalcitonin assay. A further tumour marker assayed was CEA, levels of which are raised in the presence of thyroid neoplasms at an advanced or metastasizing stage. The authors conclude by presenting the results obtained and confirm the usefulness of these tumour markers in the study and follow-up of patients with thyroid carcinoma.

Adenocarcinoma↗

Lessons from Chernobyl: the event, the aftermath fallout: radioactive, political, social.

The accident at the Chernobyl nuclear power station on April 26, 1986, released about 300 MCi of radioactive substances, including about 40 MCi of 131I and 100 MCi of short-lived radioiodines. In the immediate surroundings there were 143 cases of acute radiation syndrome, 34 deaths, and hundreds of thousands of people displaced from their homes, many permanently. The social and psychologic stresses that followed have been enormous and long-lasting. This article focuses on the rising incidence of thyroid cancer in exposed children. Radiation-induced thyroid cancer following external radiation is well documented but there is little evidence in humans of thyroid cancer from internal radiation and the risk coefficient for radioiodine exposure is known. To achieve this, thyroid dose reconstruction and prospective follow-up of about 50,000 persons who were children in 1986 will be required. Thyroid cancer in children of southern Belarus began to increase in 1990 and there now are about 1,000 cases in Belarus and northern Ukraine. These aggressively growing tumors, almost all variants of papillary thyroid cancer, are typical for thyroid cancer in children not exposed to radiation, and a low mortality rate is to be expected. It also is expected, however, that malignant as well as benign thyroid neoplasms will continue to arise in these exposed children well into their adult life.

Adult↗

bcl-2, p53 and proliferating cell nuclear antigen expression is related to the degree of differentiation in thyroid carcinomas.

Thyroid carcinomas are heterogeneous in terms of histology, clinical presentation, treatment response and prognosis. Since bcl-2 and p53 gene alterations are frequently involved in both lymphoid and epithelial malignancies, we analysed the expression of bcl-2, p53 and proliferating cell nuclear antigen (PCNA) in a group of 134 patients with thyroid neoplasms. The same markers were evaluated in fetal and adult normal thyroids as well as in 40 benign lesions. The study was carried out by immunocytochemistry on archival material using antibodies against bcl-2 and p53 protein on tissue sections of 40 adenomas (As), 20 medullary carcinomas (MCs), 70 well-differentiated carcinomas (WDCs), 20 poorly differentiated carcinomas (PDCs) and 24 undifferentiated carcinomas (UCs). bcl-2 immunoreactivity was detected in 36 out of 40 (90%) As, 20 out of 20 (100%) MCs, 60 out of 70 (85.7%) WDCs, 20 out of 20 (100%) PDCs, and 8 out of 24 (33.3%) of UCs. p53 expression was present in 11.4% of WDCs, 5% of PDCs, 5% of MCs and 62.5% of UCs. By contrast, no p53 immunoreactivity was detected in 40 adenomas and in all the normal thyroid tissues studied. We observed a positive correlation between the expression of p53 and PCNA (r = 0.42; P = 0.035) in a group of UCs, but not in WDCs, PDCs and MCs. Neither p53 nor bcl-2 expression were correlated with clinicopathological parameters, such as age, sex, pTNM and survival. Our results suggest that in tumours of the follicular epithelium p53 and bcl-2 protein abnormalities are associated with more advanced carcinomas and especially with undifferentiated carcinomas, while they are only rarely altered in tumours of the parafollicular C cells.

Aged↗

Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions.

BACKGROUND: Thyroid cancer is the most common endocrine malignant disease, but preoperative diagnosis remains a challenge. Fine-needle aspiration cytology has greatly improved the clinical management of thyroid nodules, but the preoperative characterisation of follicular lesions is very difficult. Many patients are thus referred to surgery more for diagnosis than for therapeutic necessity. We undertook an international multicentre study to assess the usefulness of immunohistocytochemical staining for two potential markers of malignant thyrocytes. METHODS: Expression of galectin-3 and CD44v6 was tested on 1009 thyroid lesions (tissue specimens and cytological cell-blocks) and 226 fresh cytological samples obtained preoperatively by ultrasound-guided fine-needle aspiration of thyroid nodules (prospective analysis). The test used monoclonal antibodies specific for CD44v6 and galectin-3, the indirect avidin-biotin complex immunoperoxidase method, and 3-amino-9-ethyl-carbazole as substrate. FINDINGS: The sensitivity, specificity, positive predictive value, and diagnostic accuracy of this test method (for coexpression of the two markers) in the prospective analysis were 88%, 98%, 91%, and 97%, respectively. The sensitivity and specificity of galectin-3 immunodetection alone in discriminating benign from malignant thyroid lesions were more than 99% and 98% respectively, and the positive predictive value and diagnostic accuracy were 92% and 99%. INTERPRETATION: The integration of galectin-3 immunostaining with conventional cytomorphological and clinical diagnostic procedures represents a sensitive and reliable diagnostic approach for preoperative identification of thyroid carcinomas. This test method improves the diagnostic accuracy of conventional cytology and provides the molecular basis for a new nosological assignation of the not yet classified thyroid neoplasms of indeterminate malignant behaviour.

Antigens, Differentiation↗

Ectopic expression of a mutant form of PKCalpha originally found in human tumors: aberrant subcellular translocation and effects on growth control.

A point mutation in PKCalpha was originally discovered in a subpopulation of human pituitary tumors characterized by their invasive phenotype, and the same mutation was also seen in some thyroid neoplasms. To investigate the role of this mutation in tumorigenesis, normal and mutant human PKCalpha cDNAs were overexpressed in Rat6 embryo fibroblasts (R6). When extracts of R6 cells that expressed either the normal or mutant PKCalpha were assayed in the presence of calcium, phosphatidylserine and the phorbol ester TPA, for phosphorylation of either histone IIIS or the EGF-receptor peptide, both extracts gave similar results. However, the subcellular localization of the two proteins differed. Immunohistochemistry studies indicated that after treatment with TPA normal PKCalpha mainly translocated to the plasma membrane, but mutant PKCalpha translocated mainly to the perinuclear region and slightly to the nucleus. Furthermore, the cells that expressed the mutant PKCalpha displayed a decreased requirement for serum when compared to the cells expressing the normal human PKCalpha, and they formed small colonies in soft agar. By contrast, the cells expressing the normal human PKCalpha failed to form colonies in soft-agar. Thus, ectopic expression in rat fibroblasts of this mutant human PKCalpha sequence alters the growth properties of these cells and, when activated, the mutant PKCalpha displays aberrant intracellular translocation. Therefore, this mutation in PKCalpha could contribute to the process of tumor progression in certain human tumors.

Animals↗

S-100 protein+ dendritic cells and CD34+ dendritic interstitial cells in thyroid lesions.

Dendritic cells (DCs) are antigen-presenting cells and mature from precursor CD34+ stromal cells (dendritic interstitial cells [DICs]) or monocytes. The aim of the present study was to gain insight into the local immune response to various thyroid lesions. We investigated, immunohistochemically, the presence of S-100+ DCs and CD34+ DICs in 13 papillary carcinomas, 10 follicular carcinomas, 7 follicular adenomas, 1 Hurthle cell carcinoma, 1 Hurthle cell adenoma, 2 medullary carcinomas, 6 undifferentiated carcinomas, and 3 nodular goiters. Dense infiltrates of S-100+ DCs were noted in the majority of papillary carcinomas (mean: 66.4), while moderate infiltrates were observed in follicular adenomas (mean: 23.3), follicular carcinomas (mean: 23.5), and undifferentiated carcinomas (mean: 31.6). The remaining lesions showed slight infiltrates of scattered DCs. DICs were noted exclusively in neoplastic lesions, specifically at the periphery and within the tumor capsule. The increased number of DCs in papillary carcinomas is possibly correlated with their good prognosis. The specific distribution of DICs suggests a possible contribution to growth regulation of thyroid neoplasms.

Adenoma↗

Hyperthyroidism and concurrent thyroid carcinoma.

In the last twenty years, medical studies have reported a significant increase in thyroid neoplasms among patients with hyperthyroidism. Aim of the present work is to reconsider the real incidence of this not uncommon association and to establish a model for surgical treatment of hyperthyroidism for a possible concurrence with thyroid carcinoma. At the Department of Surgical Sciences and Applied Medical Technologies "La Sapienza" Rome's University, during the period 1994 to 1999, an homogeneous group of 82 patients was surgically treated for hyperthyroidism. Of our patients, fifty-four (66%) had a "multinodular toxic goiter" (MTG), twenty (24%) a "functional autonomous nodule" (FAN) while the remaining patients were affected by Graves' disease. The surgical procedures adopted were: 1) total extracapsular ipsilateral lobectomies and isthmectomies in sixteen patients with FAN; 2) total extracapsular thyroidectomy in all patients with MTG and with Graves' disease and in the remaining four patients with FAN after a long time treatment with thyrostatic drugs. On six (7%) of our patients we found out a thyroid carcinoma: five with MTG and one with Graves' disease. However, no association with thyroid carcinoma was observed in anyone with FAN. The correct treatment of thyroid surgical diseases is a single definitive operative approach. The procedure must be a total thyroidectomy in MTG and Graves' disease. However, in patients with FAN it's possible, after careful evaluation, to carry out a total extracapsular ipsilateral lobectomy with isthmectomy, justified by the normal morphology of the remaining thyroid tissue. It is always possible, in these cases, a subsequent complete exeresis if a carcinoma is present in the removed lobe.

Aged↗

Fine-needle aspiration cytodiagnosis of the "cold" thyroid nodule.

The results of 1886 fine-needle cytoaspirations of solid, palpable thyroid nodules, "cold" on scintiscanning, performed between 1 January 1978 and 31 December 1986, were analyzed. In total 36 diagnoses of malignancy were made (1.9%). The results of cytologic and histologic examinations were compared in 114 cases to verify the diagnostic accuracy of this method; there was agreement in 98 cases and discordance in 16 consisting of 13 false negatives (11.4%) and 3 false positives (2.6%). The sensitivity was 77.9%, specificity 94.5%, positive predictive value 93.8%, negative predictive value 80% and test efficiency 86%. These values are in the range of those reported in the literature and confirm the validity of fine-needle aspiration cytology in the preoperative diagnosis of thyroid neoplasms.

Adolescent↗

Psammoma bodies in fine needle aspirates from thyroids containing nontoxic hyperplastic nodular goiters.

Psammoma bodies present in fine needle aspiration (FNA) smears with typical cytologic features of colloid goiter from five patients raised the possibility of coexistent papillary carcinoma. However, subsequent careful histologic examination of the entire thyroidectomy specimens did not show occult carcinoma in any of the cases. The psammoma bodies were identified in the stroma next to the foci of papillary hyperplasia in each case. They were small, often equal in size to or slightly larger than the follicular epithelial cell nuclei, and could be misinterpreted as epithelial cell nuclei. These findings suggest that the presence of psammoma bodies in an FNA smear cytologically consistent with a colloid goiter should raise the possibility of coexistent papillary hyperplasia or neoplasia. However, because of the strong statistical association of psammoma bodies with malignant thyroid neoplasms, histologic confirmation is mandatory in such cases.

Adult↗