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Papillary carcinoma of the thyroid (PTC) is generally a slow growing tumor with favorable prognosis, while anaplastic thyroid carcinoma (ATC) is highly aggressive malignancy. Genetic defects in apoptotic pathways may contribute to differences in their biological behavior. In this study, we analyzed immunohistochemically the expression of apoptosis-related molecules: galectin-3, Bcl-2, survivin (antiapoptotic), and Bax (pro-apoptotic), in archival tissue sections of PTC (n = 69) and ATC (n = 30) and correlated the results with clinicopathological parameters of these tumors. Galectin-3 and Bcl-2 showed a similar trend of down-regulation from high levels of both in PTC to low levels in ATC (p

OBJECTIVE We aimed to investigate the role of caveolin-1 in papillary thyroid carcinoma pathogenesis. STUDY DESIGN Case series with chart review. SETTING Institute for the Application of Nuclear Energy. SUBJECTS AND METHODS We evaluated the expression of caveolin-1 in papillary thyroid carcinoma (PTC) by Western blot (WB) and compared the findings with immunohistochemical (IHC) expression of both epithelial and stromal caveolin-1 on the corresponding histological specimens. The results were related to clinicopathological features and BRAF mutation status. RESULTS Caveolin-1 expression was found in malignant thyroid epithelium and more abundantly in tumor stroma but varied in both compartments within and between PTC subtypes. Caveolin-1 expression in the epithelium was more intense in classical PTC than in the other histological types. On the contrary, stromal caveolin-1 expression was stronger in the follicular, solid, and trabecular PTC variants than in classical PTC. Trends for down-regulation of caveolin-1 expression in epithelium and up-regulation in stroma from the classical via follicular to the solid variant were observed. The relation of WB and IHC results with clinicopathological parameters showed lower caveolin-1 tissue content in BRAF mutated tumors (P < .05), a positive correlation of epithelial caveolin-1 expression with lymph node metastasis (P < .05), and a negative association of stromal caveolin-1 expression with the degree of neoplastic infiltration and BRAF status. CONCLUSION Altered expression of caveolin-1 in the thyroid epithelial and stromal compartments may be involved in the pathogenesis of PTC. The potential clinical significance of caveolin-1 expression, as well as its relation to BRAF mutation status, deserves further investigation.

OBJECTIVE: Serum calcitonin (CT) is a sensitive but not specific marker for medullary thyroid carcinoma (MTC). There are a large number of conditions that may elevate CT levels. CASE REPORT: Herein we present the case of a 47-year old woman with Hashimoto thyroiditis, goiter, cervical lymphadenopathy and high CT and CEA levels. After surgical extirpation of the lymph node neuroendocrine cancer metastasis was suspected. Computed tomography of the chest showed a tumor mass on the right lung. Bronchoscopy was performed and pathological and immunohistochemical analysis revealed large cell neuroendocrine lung cancer (LCNEC). After chemotherapy, significant reduction of tumor mass was achieved with a moderate decrease in CT levels in parallel. CONCLUSIONS: We present a female with LCNEC, a condition which is usually observed in older men (7th decade) and is not associated with CT secretion. Hashimoto thyroiditis is associated with increased incidence of different types of cancers (e.g. thyroid, colon). No reports at present exist on the incidence of lung cancers in patients with thyroid disease.

Cytological analysis of fine-needle aspiration (FNA) is the first step in evaluation of patients with nodular thyroid disease with the primary goal to exclude thyroid malignancy. Its improvement by combining cytology with molecular markers is still a matter of investigation. In this study, 2 molecular markers were used: caveolin-1 and epidermal growth factor receptor (EGFR), along with the well-established genetic marker BRAF V600E mutation. We set out to determine the expression signatures of EGFR and caveolin-1 in patients with thyroid malignancy as well as to determine their possible association with disease severity. In FNA biopsy samples (n=186), immunocytochemical expression of caveolin-1 and BRAF V600E mutation coincided with malignancy. The patients were sorted according to 3 parameters: final histopathological diagnosis, caveolin-1 expression, and BRAF V600E mutation status before measurement of EGFR mRNA expression. EGFR upregulation was detected in the group of patients with malignant diagnosis, no caveolin-1 expression, and wild-type BRAF. Spearman rank correlation yielded a statistically significant negative correlation of EGFR and caveolin-1. Double immunofluorescence confirmed colocalization and inverse expression of EGFR and caveolin-1. Our data demonstrated that EGFR overexpression is associated with malignancy but not with tumor aggressiveness. Furthermore, high-caveolin-1/low-EGFR cases were associated with an advanced pT status and had a greater degree of neoplastic infiltration than low-caveolin-1/high-EGFR cases. Combining caveolin-1 and BRAF V600E with EGFR might help in recognizing more aggressive thyroid lesions in a pool of relatively indolent tumors in FNA biopsies and thus be useful for early risk stratification of thyroid cancer patients.

The most common histological variants of papillary thyroid carcinoma (PTC), classical (CPTC) and follicular (FPTC), have different diagnostic features, molecular biology, and prognosis. Matrix metalloproteinase-9 (MMP-9) endopeptidase which degrades the components of the extracellular matrix is essential in the invasive growth and metastasizing of malignant tumors. The serum copper (Cu)/zinc (Zn) ratios are sensitive diagnostic and prognostic indicators in oncology since Cu- and Zn-dependent enzymes play important roles in the genesis and the progression of tumors. The aim of this study was to examine the expressions of MMP-9 in tissues of CPTC and FPTC, as well as to determine the Cu/Zn ratios in the same samples. MMP-9 was determined immunohistochemically, and the concentrations of copper and zinc in thyroid tissue were determined by means of flame atomic absorption spectrometry. The results obtained revealed significantly higher expressions of MMP-9 in CPTC in comparison with FPTC, as well as higher Cu/Zn ratios in CPTC than in FPTC. Thus, determining MMP-9 activities and the Cu/Zn ratios could improve the accuracy of the standard histopathological diagnosis of these two types of PTC.

We evaluated some proposed molecular thyroid tumor markers: thyroid peroxidase (TPO), galectin-3, cytokeratin-19, and HBME-1, individually and in combination, by immunohistochemistry in a total of 242 archival thyroid tissue sections. The expression of each individual marker was most helpful for the diagnosis of papillary carcinoma and its follicular variant. However, none of them was sensitive and specific enough to discriminate between Hurthle adenoma and carcinoma. Galectin-3 and HBME-1 could be used as single discriminators between follicular thyroid adenoma and carcinoma, but HBME-1 is the better choice. As a single test, all analyzed tumor markers had sufficient power to predict differentiated thyroid cancer, with sensitivities ranging from 66.5% to 82.2%. The sensitivity was improved by using combinations of some proposed markers. Only two antigens, HBME-1 and TPO, had distinct predictive values for different diagnostic alternatives i.e. a sequential combination improved diagnostic accuracy between follicular thyroid adenoma and the follicular variant of papillary thyroid carcinoma to 92.6% and consequently, between overall benign and malignant thyroid tumors to 89.1%. HBME-1 is the most accurate ancillary stain in discriminating well-differentiated thyroid carcinomas from benign tumors, although the addition of TPO did improve accuracy and served as a useful confirmatory marker.

Fine-needle aspiration biopsy (FNAB) plays an important role in the evaluation of thyroid nodules and the selection of patients for surgical treatment. It is complementary with clinical, ultrasonographical, radionuclid and radiographic investigations in the assessment of true nature of thyroid nodule. Cytological findings can be classified as non-representative, suspicious, benign or malignant or into 8 diagnostic categories: benign colloid nodules, cystis lesions, different types of thyroiditis, cellular microfollicular lesions, Hurthle-cell lesions, primary malignant tumors, other lesions and the non-diagnostic category. FNAB is successful in the diagnosis of benign cystic thyroid lesions, Hashimoto thyroiditis, anaplastic and papillary thyroid carcinoma, while it is less precise in the diagnosis of medullary carcinoma, lymphoma and secondary thyroid tumors. Follicular, as well as, Hurthle-cell thyroid carcinoma cannot be cytologically differentiated from follicular and Hurthle-cell adenoma of the thyroid gland. Immunocytochemistry may facilitate the diagnosis of thyroid tumors with follicular origin, applying galectin-3, cytokeratin 19 and HBME-1, whereas medullary thyroid carcinoma is typically proved with calcitonin immunostaining.

The aim of this study was to assess the clinical utility of circulating preoperative Cyfra 21.1 [soluble fragment of cytokeratin (CK) 19] and galectin-3 (gal-3) in patients with thyroid tumors, to compare their serum values with tissue expression and to analyze the prognostic significance of these markers in relation to the clinical status of postsurgical differentiated thyroid carcinoma (DTC) patients.Concentrations of Cyfra 21.1 and gal-3 were evaluated by immunoassays in sera of 9 healthy subjects, 97 preoperative patients with diverse thyroid tumors (10 FTA, 63 PTC, 11 FTC, 5 PDTC, 4 ATC, 4 LNM) and 25 postoperative DTC patients (14 remissions and 11 metastases).Low Cyfra 21.1 values were found in all subgroups, but with a tendency toward higher values in poorly differentiated DTC patients. Compared to the control (0.23 ng/mL), serum levels of gal-3 were significantly elevated in patients with thyroid tumors but with overlapping between adenoma (4.16 ng/mL) and carcinoma (3.85, 4.37, 4.64, 6.07 ng/mL for PTC, PDTC, ATC and LNM, respectively). The tissue expression of CK19 and gal-3 was immunohistochemically determined on 45 matched paraffin-embedded sections. Most thyroid carcinomas showed positive CK19 (27/35) and gal-3 immunostaining (31/35), while adenomas were mostly immunonegative (8/10 and 7/10, respectively). However, there was no significant correlation between their serum and tissue levels. Clinical status of postoperative DTC patients had no influence on serum concentrations of the tested markers.While CK19 and gal-3 are accurate as tissue markers, their serum levels could not be used as reliable markers for identification of thyroid malignancy or in thyroid cancer follow-up. On the other hand, a tendency toward higher serum levels of Cyfra 21.1 in the small number of PDTC patients examined adds weight to previous reports postulating a role for cytokeratins in predicting a high degree of malignancy.

Background/Aim. The major one among the procedures for evaluating changes in the thyroid nodules is fine needle aspiration biopsy (FNAB). Thyroid scintigraphy is commonly used in diagnostic algoritham of nodules. Less than 5% of examined nodules show to be malignant. Scintigraphically, nodules could be classified as functional and nonfunctional. It is estimated that the risk of malignacy in nonfunctional nodules ranges from 8% to 25% and more. Aspiration punction provides 100% specific and positive predictive value. The aim of the study was to establish the distribution of cytological findings in nonfunctioning thyroid nodules. Methods. The prospective study enrolled 112 patients, 104 women and 8 men, submitted to thyroid scintigraphy for known thyroid nodule disorder. Scintigraphy was performed about half an hour after iv administration of 74 MBq of sodium-pertehnetate. A pin hole collimator was used. Scintigrams were visually evaluated, and absence of radiopharmaceutic in a nodule was estimated as nonfunctional one. Such nodules were afterwards subjected to FNAB and material obtained was cytologically analyzed. Results. In our patients nonfunctioning nodules comprised tissue of colloid struma, thyroid cyst, regular thyroid tissue, follicular lesion, oxiphillic lesion, papillary carcinoma tissue and tissue of lymphocytic thyroiditis. The most frequent cytological finding were colloid cysts (52%). A total of 70% were female nodules. Five citological findings were histopathologically analyzed. Conclusion. Cytological finding of nonfunctional nodules determines of the decision on radical therapy, and our preliminary results imply the need of FNAB routine use in nuclear medicine practice.

The expression of galectin-8 (gal-8) has been shown to be altered during neoplastic transformation of certain cell types. This is the first study aimed to analyze the expression of this protein in normal and pathological human thyroid tissue. A total of 41 archival thyroid tissue samples (5 follicular adenomas, 31 papillary carcinomas, 5 follicular carcinomas) together with 36 adjacent hyperplastic or normal thyroid tissues were analyzed by immunohistochemistry. Galectin-8 was expressed in the majority of papillary carcinomas (27/31; 87%). Positive but weaker staining was also found in some of the follicular thyroid carcinomas (2/5; 40%) and adenomas (2/5; 40%). This protein was not detectable in five normal thyroid tissue samples, whereas hyperplastic areas adjacent to tumor were weakly positive in 9 out of 31 cases (29%). High gal-8 immunostaining in papillary thyroid carcinoma indicates that gal-8 may potentially serve as a marker of papillary thyroid carcinoma. However, it does not seem to be helpful in the differential diagnostics of follicular carcinoma and adenoma. Further studies are required to determine biological functions and molecular mechanisms underlying the increased expression of gal-8 protein in thyroid lesions, particularly, in papillary thyroid carcinoma.

Thyroperoxidase and galectin-3 have been reported as useful immunohistochemical markers of thyroid malignancy. In this study, we evaluated the relationship between immunohistochemical staining results for these markers and clinicopathologic features of patients with differentiated thyroid cancer. A total of 193 archival thyroid samples including 28 follicular adenomas, 18 follicular carcinomas, and 147 papillary carcinomas with 114 adjacent thyroid tissues were analyzed by immunohistochemistry. Thyroperoxidase was underexpressed (50% stained thyrocytes), and galectin-3 was expressed (5% stained thyrocytes) in most carcinomas. The sensitivity for diagnosis of differentiated thyroid carcinoma was 86.1% for thyroperoxidase and 82.4% for galectin-3, whereas the combination of both markers increased the sensitivity up to 94.5%. Thus, the combination of thyroperoxidase and galectin-3 immunohistochemistry may help to ascertain the malignant nature of the lesion. Furthermore, tumor size, nodal involvement, extrathyroidal invasion, and high tumor-node-metastasis stage in patients with papillary carcinoma were related to thyroperoxidase absence and high galectin-3 expression in most cases (P.05). In patients with follicular carcinoma, the extent of invasiveness was associated with galectin-3 positivity. Thus, expression of these markers is related to more or less aggressive biological behavior of differentiated thyroid carcinomas. Although thyroperoxidase presence may indicate favorable prognosis of papillary cancer, expression of galectin-3 illustrates the potential importance of this protein in the pathogenesis and/or progression of differentiated thyroid carcinomas.

Background Nodular follicular lesions of thyroid gland comprise benign and malignant neoplasms, as well as some forms of hyperplasia. “Follicular” refers to origin of cells and in the same time to growth pattern - building follicles. Nodular follicular thyroid lesions have in common many morphological features, therefore attempts were made to define additional criteria for distinction between follicular adenoma, follicular carcinoma and follicular variant of papillary carcinoma. Increasing number of immunohistochemical markers is in the continual process of evaluation. Methods Tissue microarrays incorporating, total 201 cases, out of which 122 malignant and 79 benign follicular lesions, including neoplastic and non-neoplastic, were constructed and immunostained with antibodies to CD56, CK19, Galectin-3, HBME-1. Tissue cores were exclusively being acquired from tumour/lesion on interface with normal thyroid tissue. A systematic review of literature was done for period from the year 2001 to present time. Results All analysed markers may make a difference between benign lesions/tumours from differentiated thyroid carcinomas (p =

Thyroperoxidase (TPO) is a thyroid-specific enzyme expressed by differentiated thyroid cells. Initial immunohistochemical studies claimed that TPO expression, detected by the monoclonal antibody mAb 47, may be a potentially important diagnostic tool in differentiating malignant from benign lesions. However, some recent studies have failed to reproduce the earlier results, suggesting the limitations for TPO immunohistochemistry. To assess these observations we have evaluated the immunohistochemical expression of TPO in thyroid tissue from 215 patients. The studied material included 87 nonmalignant thyroid lesions and 128 thyroid carcinomas. TPO expression was investigated using newly available mAb 47 and staining of less than 80% of the follicular cells/specimen as the threshold indicating a malignant lesion. We found that TPO had a sensitivity of 89.9% for cancer and a specificity of 64.4% for nonmalignant lesions, showing that it does not give a sufficient degree of diagnostic certainty that the lesion is benign. In addition, the variability in the degree of TPO expression found within and between follicular carcinomas, and the significant number of benign adenomas having similar immunostaining patterns, assured us that TPO immunostaining is not sufficiently discriminatory in the differential diagnosis of thyroid cancer versus benign lesions.

Background. Galectin-3 has been recently recog-nized as a promising presurgical marker of thyroid malignancy.Methods. Galectin-3 expression was examined immunohis-tochemically in 202 specimens of papillary thyroid carcinoma(PTC) in relation to histomorphologic subtypes and clinicopatho-logic data.Results. The sensitivity of galectin-3 immunostaining versusconventional histology was 98% (100 of 102) for classical PTC,85.2% (46 of 54) for follicular variant, and 50% (23 of 46) forfollicular/solid variant of PTC. All cases (n = 36) involving lymphnode metastases and 42 of 45 cases with extrathyroid invasionexpressed galectin-3. However, among the galectin-3–positivecases (n = 169), 133 were without lymph node metastases, and127 were without extrathyroid invasion. Galectin-3 expressionwas not related to the size of intrathyroid PTC.Conclusions. Galectin-3 immunohistochemical expressionitself is not an indicator of local metastatic spread or extrathyroidinvasion of PTC, thus being irrelevant clinically from this aspect.Galectin-3 is an excellent marker for classical PTC but must beused with caution in diagnosing unconventional variants of PTCbecause of the possibility of false-negative results. A 2005 WileyPeriodicals, Inc. Head Neck 27: 1049–1055, 2005Keywords: galectin-3; thyroid; papillary carcinoma; immunohis-tochemistry; tumor marker

Follicular thyroid cancer is the second most common thyroid malignancy. This tumor has a predisposition for hematogenous dissemination an extrathyroid spread. Accurate cytological diagnosis of follicular thyroid cancer is not possible and this fact highlights the necessity for surgical treatment of any suspicious thyroid nodule. Aggressiveness of this tumor is greater than in the case of papillary thyroid cancer and it is the reason for radical surgical treatment of follicular thyroid cancer. Total thyroidectomy facilitates later adjuvant therapy with thyroid hormones and radioiodine. This procedure improves the outcome and the risk of relapse. Results of our study clearly demonstrate that diagnosis of follicular thyroid cancer in us is established in the early phase of the disease (78.57%), but the significant number of the patients (21.43%) is still in the advanced phase of the disease.

Few subjects in endocrine surgery have generated as much contraversy as the management of thyroid nodule. The contraversial issues include evaluation of labaratory findings and imaging diagnostic procedures in the patient with solitary thyroid nodule. The major issue in relation to controversies is choice of optimal diagnostic workup.

The aim of the study was to show the standards of preoperative management, intraoperative monitoring and postoperative evaluation of patients with thyroid gland carcinoma. It was point out the importance of the preoperative diagnosis of the tumor, and the concurrent diseases. The special attention was paid to difficult airway recognition and resolving this situation. Both, anesthetist?s and surgeon?s point of view of perioperative and postoperative complications were discussed with special interest on early surgical complications and the need for urgent anesthetic treatment. Criteria for minimal and desirable monitoring of vital functions were suggested in order to prevent, recognize and cure complications. Our conclusions were based on recent references from the world literature and on our own experience in Center for endocrine surgery KCS, Belgrade.

Numerous pathohistologic criteria, difficultes and pitfalls in the process of diagnosing of thyroid carcinoma are discussed. Benign hyperplastic papillae may be present in colloidal cystic goiter and hyperplastic goiter. These structures are lined by cells with normochromatic nuclei and do not disturb the thyroid tissue architecture. Papillae in papillary thyroid carcinoma have cells with ground-glass, hypochromatic nuclei. Follicles inspissated in capsula of follicular or even colloidal adenoma may be evaluated as capsular invasion - diagnostic feature of follicular carcinoma. Undifferentiated thyroid carcinoma is sometimes similar to fibrosarcoma and reveal cellular pleomorphism, anaplasia and numerous foci of necrosis. Medullary thyroid carcinoma with scanty stromal amyloid, its papillary variant and carcinoid-like histologic type consist of oval cells with eosinophilic cytoplasm and dark nuclei.

Galectin-3 is a a beta-galactoside binding protein recently proposed to be a promising presurgical molecular marker for distinguishing benign from malignant thyroid neoplasms. We analyzed galectin-3 expression immunohistochemically in papillary areas of hyperplastic lesions of benign thyroid tissue in comparison with malignant papillary projections of papillary thyroid carcinoma (PTC). A monoclonal antibody to galectin-3 and ABC immunohistochemical technique were used to evaluate galectin-3 expression in 26 cases of benign papillary hyperplasia (8 cases of hyperplastic adenoma, 8 cases of hyperplastic colloid goiter, 10 cases of Graves disease) in comparison with 25 cases of PTC. Immunohistochemical results showed no reactivity for galectin-3 in papillary areas of benign hyperplastic lesions. Strong cytoplasmic galectin-3 immunoreactivity was found in all 25 cases of PTC. These results show that galectin-3 expression is a feature of malignant papillary projections but not of benign papillary hyperplasia. Thus, the immunohistochemical evaluation of galectin-3 might contribute to differential diagnosis between malignant and benign thyroid lesions with papillary projections.

The aim of the present paper was to study some characteristics and posibility of surgery of anaplastic thyroid cancer. During five years period in Center for endocrine surgery, we found anaplastic thyroid cancer in 65 patienst (44 female and 21 male), median age 63 years (from 37 to 88 years). Surgical treatment was peerformed in one half (32) anaplastic thyroid cancer patients, at majority of them operative biopsy or tumor reduction only. Radical syrgery was performed in about 10% patients. Posibility of surgery in anaplastic thyroid cancer are very limited. In one third patients there were longstanding goter or thyroid nodul or histological verified dediferentiation of papillary thyroid cancer. This patienst should be operated formerly, before anaplastic transformation.

Medullary thyroid cancer (MTC) is uncommon thyroid tumor with specific characteristics which undoubtedly divide this tumor from other thyroid malignances. Patients with sporadic or hereditary form of MTC differ in clinical presentation, recurrence of the disease and outcome. The aim of study was to establish surgical characteristics of MTC as well as clinical factors that influence surgical treatment. The study group consisted of 68 patients with MTC managed at the Center for Endocrine Surgery between 1987. and 1999. Retrospective analysis included clinical form of the disease, general data, histological and other tumor characteristics. Mean age of the patients were 47.3 years (female/male ratio: 1.5:1). Mean size of tumor was 80.5 cm3, 72.1% patients had tumor greater than 4 cm. in diameter or extrathyroid spread. The majority of patients were in II and III stadium of the disease. Primary operation (at least total thyroidectomy) was performed in 57 (84%) patients. 2(3%) had postoperatively temporally nerve palsy and 7(10.29%) temporally hypoparathyroidism. The overall survival was 46.8 + 9.9% after 9 years and 63.6 + 7.2% at 5 years. Postoperative calcitonin value is significant predictor of survival /Spearman's coefficient (R=0.7048)/, worse prognosis is in correlation with high postoperative calcitonin values. The treatment of choice is at least total thyroidectomy and central lymph nodes resection if enlarged lymph nodes are found. Precise operative technique lowers the risk of postoperative complications. Complex approach to the patient with MTC includes all available methods in pre and postoperative evaluation as well as surgeon's knowledge and skill.

Primary thyroid lymphomas are rare. Surgery is seldom indicated. The aim of the study is to find out the main characteristics of primary thyroid lymphomas in our patients, indications for surgery and the possibility of treatment, frequency and characteristics of rare thyroid tumors. Method: retrospective study of 1044 patient operated for malignant thyroid tumor. Results: From 1995 to may 2003, we operated upon 15 patients with primary thyroid lymphomas, 2 men and 13 women mean age of 50.12 years (from 22 to 74 years), also one patient of age 69 with insular thyroid cancer. Reason for surgery was thyroid tumor in all, compressive disturbances in 9, among them 4 with asphyxia. Radical total thyroidectomy was performed in 4 (26.7%), whole in others some residual tumor tissue was could not be removed in spite of thyroidectomy in 3, hemithyroidectomy in 2, tumor debulking in 5 and only open biopsy was performed in one patient. There was no operative mortality, no postoperative hypocalcaemia and no recurrent nerve palsy. Histological type of tumor was Non-Hodgkin lymphoma in 13 patients, Hodgkin disease in 2 female patients of age 22 and 24. Hashimoto thyroiditis was present in 3 patients. After surgery, 13 patients were treated with chemotherapy, one patient died one month after the operation and one patient refused chemotherapy. Follow-up data are available for 9 patients and the mean follow-up period was 20 months (1-48months). Three patients died after a month, 2 and 3 years after surgery. Six patients are without local relapse. In one patient who refused chemotherapy, a year after thyroid surgery, resection of large intestine was performed because of lymphoma of the colon. Conclusion: Malignant thyroid lymphomas are rare. They present with rapidly growing thyroid tumor, compression and asphyxia. Surgery is only temporarily effective and it is necessary to start with chemo-radiotherapy as soon as possible. Rare forms of thyroid cancer have to be histological recognized in order to choose the best way of treatment.

Recurrent thyroid tumors are much less frequent but more aggressive than primary tumors. The aim is to find out their characteristics, aggressiveness and the possibility of radical surgical excision as well as the frequency of complications. Method and material: retrospective study on 69 patients operated for recurrent thyroid tumors. Results: Recurrent tumors were found in 42 patients with papillary, 11 with follicular (8 with Hurthle), 9 with medullary and 7 with anaplastic thyroid tumors. Relapse in thyroid bed on dominant side had 41 patients (59.4%), relapse on the opposite side we found in 19 patients (27.5%) and relapse in lymph nodes outside of thyroid bed in 37 patients (53.6%). In 33/69 patients, the first procedure was incomplete (reduction in 5, partial resection in 19, hemithyroidectomy in 9). The second procedure was incomplete in 14, near total thyroidectomy in 2, total thyroidectomy in 33 and dissection of lymph nodes in 33, among them in 20 with the operation in thyroid bed. Preoperative recurent nerve palsy had 2 patients and transitional recurent nerve palsy occured after second procedure in 2 patients. Among 33 patients after thyroidectomy for recurent tumor, postoperative hypoparathyroidism occured in 8 (24.2%), of whome in 2 permanent (6%). In the group of 54 patients with recurent differentiated thyroid cancer, radioiodine therapy after first operation had received only 7 patients (13%). Conclusion: the main causes of thyroid cancer relapse are incomplete first procedure and agressiveness of cancer. It is not always possible to excise the complete recurrent tumor. After surgery for papillary cancer, radioiodine therapy is seldom used.

BACKGROUND: Galectin-3, a lectin with specificity for beta galactosides, is believed to be implicated in multiple biological processes through interactions with complementary glycoconjugates. Alterations in galectin-3 expression are observed in a variety of human tumors. In thyroid, this lectin has been found to be highly expressed in malignancies of epithelial origin. We analyzed galectin-3 expression in medullary thyroid carcinoma (MTC). MATERIALS AND METHODS: An immunohistochemical study using monoclonal antibody was performed on paraffin sections of twenty cases of sporadic MTC comprising ten cases without and ten cases with lymph node metastases at the time of surgery. RESULTS: Positive cytoplasmic staining for galectin-3 was found in 16/20 cases, but varied in intensity and distribution from weak/focal (7/16) to moderate (7/16) or strong (2/16). Advanced stage of MTC (with lymph node metastases at the time of surgery) showed moderate to strong galectin-3 expression more frequently (8/10) than cases without lymph node metastases (1/10). CONCLUSION: These findings suggest that galectin-3 expression is associated with the advanced stage of disease and that this lection might play a role in the pathobiology of MTC.

Preoperative diagnosis of papillary thyroid carcinoma (PTC) comprises numerous diagnostic procedures which are mostly applicable in tertiary institutions. Normal thyroid function depends on the presence of many trace elements and copper (Cu) and zinc (Zn) are some of those. The study is based on retrospective review of 118 patients with preoperatively diagnosed benign thyroid disease (BTD) and 12 with PTC, who underwent thyroid surgery at the Center for Endocrine Surgery Clinical Center of Serbia, Belgrade, between 2010 and 2012. The objective was to evaluate concentrations of Cu and Zn in serum as possible prediction markers for PTC in patients who underwent surgery for preoperatively diagnosed BTD. Concentrations of Cu and Zn ions in serum were measured using atomic absorption spectrophotometer. Data were analyzed using methods of descriptive statistics, Anova and t-test (p

Aims Galectin-3 is a beta-galactoside binding protein involved in multiple biological processes through interactions with complementary glycoconjugates. We analysed the expression and coexpression of galectin-3 and carcinoembryonic antigen (CEA), one of the putative galectin-3 ligands, in medullary thyroid carcinoma (MTC). Methods and results An immunohistochemical study using monoclonal antibodies was performed on paraffin sections of 20 cases of sporadic MTC comprising 10 cases without and 10 cases with lymph node metastases at the time of surgery. CEA expression was found in all tumours, distributed predominantly in the cytoplasm and occasionally at the cell surface. In the majority of cases (18/20) moderate to strong intensity of staining was found in most of the cells. Positive cytoplasmic staining for galectin-3 was found in 16/20 cases, but varied in intensity and distribution from weak/focal (7/16) to moderate (7/16) or strong (2/16). More intense staining for galectin-3 was mainly associated with MTC cases involving lymph node metastases. Eight out of these 10 cases showed moderate to strong galectin-3 expression concomitant with CEA expression throughout the tumour tissue. Conclusions These findings suggest that galectin-3 might play a role in the pathobiology of MTC. Simultaneous expression of galectin-3 and CEA in the same tumour cells at an advanced stage of MTC indicates the possibility of their autocrine cooperation during tumour progression.

Fine-needle aspiration is a low-cost diagnostic tool with principal value in determining which patients with thyroid nodules should undergo surgery. Team work and close cooperation among endocrinologists, surgeons, and pathologists are essential for success. Cytologic criteria for diagnosis of the most frequent conditions (benign cystic lesions), Hashimoto thyroiditis and malignancies found in thyroid aspirates have been provided. The unsolved problem of the so-called "follicular" or oxyphilic lesion or neoplasia will be investigated by immunocytochemistry.

Cytokeratin19 (CK19) has been reported as a useful marker of thyroid tumors. We evaluated its value for differential diagnosis of thyroid neoplastic lesions and assessed its usefulness for predicting aggressive behavior of papillary thyroid carcinomas by correlating immunohistochemical results with clinicopathological features of the patients. A total of 351 thyroid tissue samples included 27 follicular adenomas (FTA), 18 follicular carcinomas (FTC), 147 papillary carcinomas (71 of follicular type-PTCfv and 76 of classical type-PTCcl) and 33 cases of anaplastic carcinoma with 126 adjacent thyroid tissues. Diagnostic usefulness of CK19 was determined by ROC analysis, while its value as a predictive marker of PTC was tested by univariate and multivariate analysis. According to ROC analysis, CK19 can discriminate both types of PTC from other neoplasias of the thyroid gland (p < 0.05). Although greatest accuracy was gained for the identification of PTCcl (91.07 %), this marker was also helpful for distinguishing PTCfv from FTA and FTC (accuracy 71.43 and 65.17 %, respectively). Regarding the univariate set of tests, high expression of CK19 correlated significantly with age, multifocality, extrathyroidal extension, pT status and pTNM stage of PTC (p < 0.05 for all). Multivariate analyses confirmed the significant association of high CK19 expression with extrathyroidal extension of PTC as well as with pTNM stage (p < 0.05 and p < 0.01, respectively). CK19 is a useful marker for the identification of both types of PTC. High expression of this protein predicts the aggressive behavior of PTC and can help in the identification of a particular subgroup of PTC patients with a potentially worse prognosis.

A 67-year-old female patient presented with visual field impairment and hyperprolactinemia. Imaging revealed a sellar and suprasellar mass and during the evaluation of the sellar lesion, papillary thyroid carcinoma (PTC) was diagnosed by fine-needle aspiration biopsy in a long-standing euthyroid multinodular goiter. The patient did not have a previous history of PTC. Total thyroidectomy confirmed the diagnosis of PTC. Due to progressive visual loss, she underwent transcranial surgery for decompression of the optic chiasm. Pituitary metastasis from PTC was confirmed, histologically and immunohistochemically. In literature, overall 13 cases, including ours, with PTC metastasis to the sellar region have been reported. Most were women, with a median age of 56 years. Two thirds of patients were previously diagnosed with PTC. The presence of other distant metastases was confirmed in less than half of the patients. Only 2 and our patient had immunohistochemical confirmation of PTC metastasis to the sellar region. The presenting signs and symptoms included: visual field defects, ophthalmoplegia, and anterior pituitary hormone deficiencies. In conclusion, this is a rare case of metastatic PTC to the sellar region unequivocally confirmed by immunohistochemistry in whom the disease first presented with a sellar and suprasellar mass.

Purposes of the study In contrast to familial medullary carcinoma, familial nonmedullary thyroid carcinoma (FNMTC) is less frequent and has been less investigated. The aim of this study was to determine the frequency of FNMTC and analyse the main demographic and clinical characteristics of the patients. Material and methods Data on 1411 patients surgically treated for nonmedullary thyroid carcinoma, in the Center for Endocrine Surgery in Belgrade, from 1995 to 2006 were analysed. The possible presence of malignant tumours of the thyroid gland was investigated in their closest relatives in order to identify cases of FNMTC. Only data on first-degree relatives (parents and children) and second-degree relatives (grandparents, grandchildren and siblings) were taken into account in the analysis. Results Thirteen patients (11 females and 2 males) (0.92% of those with nonmedullary carcinoma of the thyroid gland) had a familial form of the disease. In five families two members had a tumour, and in one family three members. In five out of six families it was a papillary carcinoma and in one family a follicular carcinoma. Patient age varied from 20 to 79 years, with a mean age of 40 years. The tumour size ranged from 5 to 60 mm (mean 25 mm). In two of the thirteen cases the tumour penetrated the capsule of the thyroid gland. In four cases the tumour was multicentric and bilateral, and in a further two metastases were present in regional lymph nodes. During the follow-up period, which lasted from 2 to 12 years (mean 8.5 years), two relapses were detected. Conclusion Familial nonmedullary carcinoma of the thyroid gland occurs very rarely.

To gain a better insight into the differences in biological behaviour between papillary microcarcinoma (PMC) and clinically evident papillary thyroid carcinoma (PTC).Immunohistochemical analysis of apoptosis related molecules (Bcl-2, Bax, p53) and proliferation related marker (PCNA) in 39 archival cases of PMC and 46 cases of PTC.Bcl-2 and Bax were expressed in most PMCs and PTCs. The average Bcl-2 staining score did not differ significantly between PMCs and PTCs (p0.05), but the average Bax score was significantly lower in PMCs (p0.05). The Bcl-2/Bax ratio was significantly higher in PMCs than in PTCs (p0.05). The expression of p53 was similar in PMCs and PTCs, without a correlation with clinical data, but was associated with high Bax expression (p0.05) in these cases in both groups. Non-malignant tissue expressed only Bcl-2, but not p53 or Bax. PCNA expression was significantly lower (p0.05) in PMC than in PTC and positively correlated with tumour size (p0.05).The higher Bcl-2/Bax ratio and lower proliferative activity in PMC suggest differences from PTC in the balance between apoptosis and proliferation. However, the presence of p53 and Bax in PMC indicates malignant potential, and thus PMC should be treated with caution.

Aims : Galectin-3 is a β-galactoside binding protein, recently recognized as a promising molecular marker of thyroid malignancy. As reported in several studies, galectin-3 is highly expressed in papillary thyroid carcinoma, but its expression has not been investigated in papillary microcarcinoma, which is a variant of papillary thyroid carcinoma. Methods and results : Using a monoclonal antibody to galectin-3 and the avidin–biotin–peroxidase complex (ABC) immunohistochemical technique, we analysed galectin-3 expression in 63 cases of papillary microcarcinoma. The results showed immunohistochemical reactivity for galectin-3 in 51 (80.9%) cases. Intensity of staining varied from strong or moderate to weak. Galectin-3 localization was mostly cytoplasmic, but also membranous or nuclear in some cells. Immunohistochemical expression of galectin-3 was not found in 12 (19.1%) cases. Most galectin-3 negative microcarcinomas (10/12) were of the non-classical type, i.e. without papillary architecture. Neither the frequency nor the intensity of a positive reaction was related to tumour size. Conclusions : Galectin-3 gene is expressed at the protein level in most papillary microcarcinomas, although with slightly lower frequency than that reported for clinically evident papillary thyroid carcinoma. The presence of galectin-3 in clinically silent microcarcinomas may indicate that galectin-3 is not related to growth or aggressiveness of papillary thyroid microcarcinomas but rather plays some other role in thyroid tumour biology.

The aim of this study was to gain better insight into molecular changes which reflect disturbances in the balance between proliferation and apoptosis during progression of thyroid malignancy from papillary microcarcinoma (PMC) via clinically manifest papillary carcinoma (PTC) to anaplastic carcinoma (ATC). The apoptosis related molecules (Bcl-2, Bax) and proliferation related marker (PCNA) were analysed immunohistochemically in 120 archival cases comprising PMC (n=34), PTC (n=52) and ATC (n=34). In addition, in situ apoptotic cell death was analysed by the TUNEL method. The average Bcl-2 staining score did not differ between PMC and PTC (p>0.05), but was significantly lower in ATC (p

Background: Secondary thyroid cancer is much less frequent than primary and in the majority of cases represents disseminated disease where operation on thyroid is useless or thyroid tumor is not operable, infiltrating surrounding structures. Methods: Five case reports of patients operated for secondary thyroid cancer. Results: Case 1: In male patient aged 64 years thyroidectomy was done for thyroid solid tumor 5 years after lung lobectomy for bronchogenic planocellular cancer. FNB suspected nonthyroid cancer histological analysis revealed planocellular cancer (Grimelius staining excluded medullar cancer) and multinodular goiter. Case 2: In female patient aged 65 years, thyroidectomy was done 4 years after left mastectomy with the history of long standing multinodular toxic goiter. Infiltrate remained in trachea and esophagus, histology revealed breast cancer metastasis in thyroid, confirmed with special mucin I, and estrogen receptor staining with negative thyroglobulin staining. Case 3: In female patient aged 76 years thyroidectomy was performed for metastatic lucidocellular kidney cancer in recurrent goiter (with Vimentin staining), a year after nephrectomy and 50 years after first goiter operation. Case 4: In female patient aged 58 years thyroidectomy was performed for planocellular infiltration of esophagus into the left thyroid lobe. Case 5: In female patient aged 77 years thyroidectomy was done for hemorrhage into thyrotoxic goiter, histology revealed metastasis of planocellular cancer of unknown origin into thyroid. Case 6: In male patient aged 54 years, thyroidectomy was done for thyroid metastatic lucidocellular cancer of kidney, 2 years after nephrectomy. Conclusion: Although prognosis of secondary thyroid cancer is poor, in rare cases aggressive surgery with adjuvant therapy may be successful.

Background: Galectin-3 is an endogenous beta-galactoside binding lectin implicated in neoplastic transformation and tumor progression. High levels of this lectin have recently been found in malignant thyroid tumors, but not in normal or benign thyroid tissue, suggesting galectin-3 as a promising presurgical marker of thyroid malignancy. Methods: We analyzed immunohistochemically galectin-3 expression in thyroid tissue using a monoclonal antibody. The total of 108 tissue specimens included 55 cases of thyroid carcinoma (30 papillary, 15 follicular, and 10 anaplastic type), 15 samples of follicular adenoma, 15 samples of normal thyroid tissue, and 23 thyroid tissue specimens from human fetuses (16 to 37 weeks of intrauterine life). Results: The results showed galectin-3 expression in 20/30 papillary carcinomas, 11/15 follicular carcinomas, 10/10 anaplastic carcinomas, and 4/15 follicular adenomas. Thyroid follicular cells in normal adult and fetal tissue were negative. Conclusions: These results further confirm that galectin-3 expression is a feature of malignant thyroid cells, and that immunohistochemical detection of galectin-3 could be useful in thyroid carcinoma diagnostics. The absence of galectin-3 in thyroid cells during fetal development suggests that galectin-3 is expressed de novo during malignant transformation of thyroid epithelium, thus it should not be considered an oncofetal antigen.

Thyroid microcarcinoma are well-differentiated tumors less than 1 cm in diameter. A retrospective analysis was performed on patients operated of benign thyroid disease at the Center for endocrine surgery, Institute of endocrinology, Clical Center of Serbia in Belgrade, from January 1st to December 31st 2004, in order to establish the incidence of microcarcinoma. Indications for surgery were euthyroid multinodular goiter in 201 patients, thyroiditis in 31, thyroid adenoma in 178, Graves disease in 89 and Plummers disease in 79 patients. The results of this study, demonstrate that in 13,4% of the patients operated for goiter, 6,4% operated for thyroiditis, 5,6% for thyroid adenomas, 9,0% for Graves disease and 7,0% of the patients operated for Plumers disease, the presence of a microcarcinoma was noticed in the definitive histopathologic examination. The results obtained are in line with the current knowledge of high incidence of thyroid microcarcinoma.