Search

Background: Current guidelines consider all cases of papillary thyroid carcinoma (PTC) smaller than 4 cm and without extrathyroidal extension (ETE) and/or lymph node metastases as belonging to the same prognostic group, and therefore the recommendation is for uniform treatment. Xing draws our attention to a small subgroup with Duet Mutations (BRAF E600 and TERT 3636 genes) that are aggressive biologically and should be treated differently. Thus the aim of the present study is to test the validity of this recommendation., Methods: A Markovian Model is used to evaluate the above hypothesis., Results: A Monte Carlo sensitivity test shows a 5.6 year survival advantage for patients with low-grade PTC, who have the Duet Mutations, and were treated by total thyroidectomy rather than hemithyroidectomy., Conclusions: We conclude that there is a place for routine molecular tests in low-risk patients with PTC., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: To review the experience of a single-center with RATS and to assess its outcome, feasibility and safety., Background: With the advent of minimally invasive techniquesin thyroid surgery, robot-assisted transaxillary thyroid surgery (RATS) has become one of the most popular approaches. Its main advantages are improved cosmetic outcome, thereby increasing patient satisfaction, improved visualization and range of motion. Several large-scale studies, have demonstrated its safety and feasibility., Methods: A retrospective review of all RATS consecutive cases at Rabin Medical Center., Results: A total of 38 RATS procedures were performed between July 2012 and May 2015. The mean age of patients was 39 years (22-74); all patients were females; the average BMI was 25 (18-32). Thirty-seven patients underwent partial thyroidectomy and one - total thyroidectomy. The average maximal diameter of nodules pre-operatively was 2.5 cm (0.5- 5). Seventeen patients (44%) had papillary carcinoma; 13 (33%) - hyperplastic nodules and 8 (20%) - benign thyroid adenomas or goiters. The average total operative time was 166 minutes. One case was converted to open due to a large tumor; there were 6 (15.7%) cases of vocal cord paresis, of which 1 (2.6%) was permanent; there were 8 (21%) cases of hypoesthesia - all resolved within 4-12 weeks. There were no cases of permanent brachial plexus injury., Conclusions: In skilled hands, RATS is a safe alternative to conservative thyroidectomy, and should be presented to patients with aesthetic concerns. As with any new emerging technique, careful patient selection is crucial and further evidence must be sought to confirm its indications over time.

Background: Medullary thyroid carcinoma management consists mainly of surgical resection and is largely chemoresistant. There is ongoing effort to discover novel therapies for medullary thyroid carcinoma. Increased levels of heat shock proteins have been associated with multiple cancers and are being studied as potential therapeutic targets. The purpose of this study was to determine the expression levels of heat shock proteins 90 and 70 and of glucose related protein 78 in medullary thyroid carcinoma tissues compared with normal thyroid tissues., Methods: 20 tissue specimens of medullary thyroid carcinoma and 10 specimens of thyroids without malignancy were analyzed by immunohistochemistry., Results: Medullary thyroid carcinoma specimens showed 27% higher expression level of heat shock protein 90 immunostaining, and a 43% higher expression level of heat shock protein 70 immunostaining versus normal controls. These differences, however, were not statistically significant. A significantly higher expression level was noted for glucose related protein 78 in the medullary thyroid carcinoma specimens than in the controls., Conclusion: This study indicates increased expression levels of heat shock proteins 90 and 70 and glucose related protein 78 levels in medullary thyroid carcinoma. These findings, though preliminary imply that these proteins may have a role in medullary thyroid carcinoma's tumor biology and may have and future therapeutic options. Larger cohorts are needed to corroborate these results., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Low-risk papillary thyroid carcinoma is commonly treated surgically. However, uncertainties exist in regard to the optimal extent of surgery. We approached this question using a decision-analysis model., Methods: A Markov model was used to compare outcome between patients with small (1-2 cm) low-risk PTC treated by hemithyroidectomy or total thyroidectomy. Probabilities and utilities were derived from the literature. The model was evaluated with Monte Carlo simulation. Sensitivity analysis was used to determine which variables most affected the model., Results: Hemithyroidectomy was associated with a minor increase in mortality risk. After incorporation of mortality risk, complications, and quality-of-life measures, hemithyroidectomy was found to be superior to total thyroidectomy, with an increasing benefit over time. Quality-of-life measures, especially disutility of disease recurrence and undergoing surgery, had the greatest effect on the incremental benefit of hemithyroidectomy., Conclusion: Based on our decision-analysis model, hemithyroidectomy is the preferred option in low-risk PTC.

Background: Treatment guidelines for well-differentiated papillary thyroid carcinoma (PTC) are based on retrospective studies and vary among professional thyroid associations., Objectives: To evaluate physician adherence to guidelines, overall and by specialty., Methods: Questionnaires on the approach to low risk PTC were distributed among 51 surgeons and endocrinologists treating patients with PTC in tertiary medical centers., Results: A wide range of answers was recorded among physicians regarding the danger posed by low risk PTC to the patient's life, urgency with which treatment should be administered, type of treatment, and risks associated with this treatment. There was a significant between-group difference in treatment preference: endocrinologists chose total thyroidectomy with radioactive iodine, while surgeons favored hemithyroidectomy alone., Conclusions: There is a wide difference in treatment recommendations between treating physicians and different specialties with regard to low risk PTC. The wide variation within and between soecialties may be explained by biases.

The value of ultrasound in detecting central compartment lymph node metastasis in patients with well-differentiated thyroid carcinoma (WDTC) is unclear. Prospective patients with WDTC attending a university-affiliated tertiary medical center between July 2010 and June 2011 underwent neck ultrasound for detection of central compartment lymph node metastases prior to surgery. Central lymph node dissection was performed during the initial surgery regardless of ultrasound findings. The sensitivity and specificity of preoperative ultrasound in detecting central lymph node metastases were calculated according to the final histopathological results. Sixty-four patients met the study criteria. Twenty-four had pathologic central compartment lymph nodes according to preoperative ultrasound, 20 of which were confirmed by histological examination. One patient was found to have pathological central lymph nodes by histology which was not detected by US. Sensitivity of preoperative ultrasound was 95%, specificity 90%, and negative and positive predictive values 97 and 83%, respectively. Preoperative ultrasound may serve as an accurate and important tool for deciding the extent of surgery in WDTC.

Objective: To identify the prognostic significance of specific lymph node related characteristics for disease persistence and recurrence in patients with pre- or intra-operative evidence of neck metastases and no other risk factors., Method and Results: Sixty-eight patients were identified; 50 per cent had persistent or recurrent disease. All underwent the same treatment strategy. There were no statistically significant differences in any of the patient- or tumour-related parameters when patients with and without persistence or recurrence were compared. Patients with recurrent or persistent disease had significantly larger (>3 cm) metastatic lymph nodes, but there were no differences regarding other lymph node related parameters (i.e. number, extracapsular extension, number of lymph nodes with extracapsular extension, and central vs lateral neck location). On multivariate analysis, however, none of the parameters were predictive of persistent or recurrent disease., Conclusion: In papillary thyroid carcinoma patients with no other risk factors, pre- or intra-operative evidence of cervical metastases was associated with a very high rate of disease persistence or recurrence. Specific lymph node characteristics were not shown to have prognostic significance.

Purpose: The natural history of papillary thyroid carcinoma (PTC) is characterized by a slow growth rate and an excellent prognosis at 20 and 30 years. However, there is a small subset of patients with poorer outcome., Methods: Twenty patients who died of PTC within 10 years of diagnosis were studied to identify prognostic indicators and biological markers of early death. Findings were statistically compared with a previous review of all patients with PTC treated in the same institute and studies in the literature., Results: The study group included 6 men and 14 women with a mean age of 65 years at diagnosis. Average tumor size was 3.6 cm; 16 patients had extracapsular extension. All tumor samples studied histologically stained poorly for p53, Ki67, and CD34. Regional metastases were present in half the patients, and distal metastases in all. All patients had an advanced disease stage (Tumor, Node, Metastases classification), and only 4 had a low score on the Metastases, Age, Completeness of resection, local Invasion, tumor Size risk stratification. Analysis of the findings against data in the literature for the whole population of patients with PTC, who had a considerably better survival (<8% mortality within 8-15 years vs 100% within 10 years in our sample), yielded significant differences for rates of extrathyroidal extension (P = .0001), regional metastases (P = .016), and distant metastases (P = .0001)., Conclusion: Extrathyroid extension, late regional metastases, and distant metastases may be risk factors for early death from PTC., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Over-expression of the proto-oncogene Akt/PKB has been demonstrated in some neuroendocrine tumor models. Akt may activate downstream proteins such as mTOR and p70S6K, inducing tumor proliferation. The rapamycin-derivative RAD001, everolimus, interacts with this pathway by antagonizing mTOR, but its effects on neuroendocrine tumors are largely unknown. We explored the mechanism of action of RAD001 on cell proliferation, hormonal secretion and on Akt/mTOR/p70S6K pathway activation, in a human medullary thyroid carcinoma (MTC) cell-line (TT) and in cells derived from human MTCs. Treatment with RAD001 significantly inhibited cell viability in a dose- and time-dependent fashion, and diminished phosphorylation of Akt downstream targets, mTOR and p70S6K, in both TT cell-line and cultured human MTCs. Akt phosphorylation was not affected by RAD001. RAD001 induced cell-cycle arrest in the G(0)/G(1) phase in TT cells, but had no effect on apoptosis. Moreover, RAD001 did not affect calcitonin and carcinoembryonic antigen secretion in TT cells and in human MTCs. RAD001 seems to have potent anti-proliferative effect in human MTC cells, which suggest that clinical trials of this agent are of considerable interest., (2009 Elsevier Ireland Ltd. All rights reserved.)

Objective: To identify prognostic factors of clinical outcome and long-term survival in medullary thyroid cancer (MTC)., Design: Retrospective case series of 51 consecutive patients (mean age 46.9 years, 57% female) treated at a single tertiary university medical center from 1970 to 2005. Medical records were reviewed for demographic data, laboratory and clinical course, treatment, and long-term outcome., Main Outcome: At presentation, 25 patients (49%) had local disease and 26 (51%) had metastatic disease (three with distant metastases). RET mutations were identified in nine of 23 patients tested. The patients with hereditary disease were younger than the patients with sporadic disease (p < 0.001) and had lower calcitonin levels at diagnosis (p = 0.004) and more multicentric tumors (p = 0.02). Initial surgery consisted of total thyroidectomy in 47 patients, with neck dissection in 26; 22 patients achieved long-term remission. The 5-, 10- and 15-year survival rates were 88%, 85%, and 77%, respectively. On univariate analysis, distant metastases during the course of the disease and elevated calcitonin levels postoperatively were significant prognostic factors of reduced survival (p = 0.001 and 0.016, respectively). Lymph node involvement at initial surgery was associated with a lower remission rate (p = 0.016) but had no impact on long-term survival (p = 0.269)., Conclusion: Patients with MTC have a generally favorable outcome, perhaps owing to recent advances in diagnosis and treatment. Although postoperative serum calcitonin level and distant metastases are the only determinants of long-term survival, the presence of cervical metastases is predictive of a higher risk of recurrent or persistent disease.

Background: Recent studies have demonstrated that cyclooxygenase-2 (COX-2) expression is associated with the carcinogenesis of numerous neoplasms. The aim of this study was to evaluate the role of COX-2 in medullary thyroid carcinoma (MTC)., Methods: Tissue specimens of thyroid neoplasms were obtained from 22 patients with MTC and 15 control subjects with nonmalignant thyroid specimens., Results: This immunohistochemical study confirms the presence of COX-2 in a significant number of MTCs. A large area of staining was noted in only 2 patients in the control group (13%) compared with 18 (82%) in the medullary carcinoma group. On a scale of 0 to 3, the average area of positive staining measured 2.35 in the study group and 0.9 in the control group (p < .0001). The average intensity of staining on a scale of 0 to 5 (deep brown) was 2.15 and 0.8 mm, respectively (p < .001)., Conclusion: COX-2 is expressed significantly in MTC including a larger area of staining and greater intensity than in nonmalignant thyroid tissue. These findings may have important treatment implications for the use of COX-2 inhibitors in patients with MTC., ((c) 2007 Wiley Periodicals, Inc. Head Neck, 2007.)

Objective: To shed light on the discrepancy between the advanced stage at presentation and high recurrence rate of well-differentiated thyroid cancer in children and the overall good survival., Design and Methods: The files of 75 children with well-differentiated thyroid cancer treated from 1954 to 2001 in a major tertiary-care hospital were reviewed for disease course, management, and outcome., Results: Sixty patients (80%) had positive neck metastases with involvement of central compartment lymph nodes in all, lateral neck nodes in 36, and distant metastases in 4. Sixty-seven patients underwent total thyroidectomy with adjuvant radioiodine treatment and 8 underwent hemithyroidectomy; all had concomitant neck treatment. The rate of local (5%) and neck (9%) recurrence was similar to the total rate reported in adults. Total thyroidectomy led to a significantly lower recurrence rate (7.5%) than hemithyroidectomy (38%; P < 0.005). Type of neck dissection did not affect recurrence or appearance of distant metastases. All deaths (n = 2) were due to distant metastases, whereas 30% of adult deaths are due to local or neck disease., Conclusions: The treatment of choice for well-differentiated thyroid cancer in young patients is total thyroidectomy. Neither regional disease at presentation nor recurrences affect survival.

Background: The determination of malignancy in follicular patterned thyroid lesions is based on postoperative histologic findings. Therefore, affected patients are referred for surgery, although only 20% will have a final diagnosis of malignancy. The aim of this study was to investigate the potential of galectin-3 as a marker of malignancy in these lesions., Methods: Fifty-four tissue specimens of follicular patterned thyroid lesions were immunohistochemically stained for galectin-3. Area and intensity scores were recorded., Results: Significant differences were found between the benign and malignant lesions. The sensitivity, specificity, positive predictive values, and negative predictive values of galectin-3 staining were 82%, 68%, 75%, and 77%, respectively (p=.0002). Significant differences were also found between the subgroups of benign and malignant lesions (p < or =.05)., Conclusions: Galectin-3 staining is highly sensitive for malignancy in follicular patterned thyroid lesions. Diagnostic problems may arise in the presence of Hurthle cell proliferation or minimally invasive follicular carcinoma.

The distinction of uncommon types of thyroid carcinomas is important, because their treatment and prognosis differ. The aim of this study was to describe retrospectively the immunohistochemical profile of uncommon types of thyroid carcinomas and mode of treatment. Of the 1194 patients with thyroid carcinomas treated in Rabin Medical Center from 1954 to 2001, 153 were uncommon types (not papillary or follicular carcinomas). Specimens from archival tissue obtained from thyroidectomies in all these cases were revised and immunohistochemically examined. Anaplastic carcinomas (n=59) were positive for high molecular weight cytokeratin (CK HMW), low molecular molecular weight cytokeratin (CK LMW), cytokeratin (CK) 7, CK 8 and 18, thymoglobulin, EMA and vimentin; medullary carcinomas (n=39) were positive for CK LMW, CK 19, CK 8 and 18, CK 10, CK 7, carcinoembryonic antigen (CEA) and calcitonin; Hurthle cell carcinomas (n=30) for CK LMW, CK 19, CK 8 and 18, thyroglobulin, epithelial membrane antigen (EMA) and CEA; squamous cell carcinomas (SCC) (n=12) for CK HMW and cytokeratin total (CKs); lymphomas (n=7) for leukocyte common antigen (LCA) and B-cells (CD 20), and clear cell carcinomas (n=6) for CK LMW, CEA and thyroglobulin. Use of an immunohistochemical panel has diagnostic value in the differentiation of uncommon types of thyroid carcinoma, which help to plan the best mode of treatment.

Background: The main limitation of fine-needle aspiration (FNA) is its limited distinction between neoplastic and benign lesions. We summarize our experience with thyroid nodules that were defined as follicular lesions by comparing the clinical and cytological features of the thyroid follicular lesions that were examined histologically to define the most reliable criteria of malignancy., Methods: The medical records of all patients who underwent thyroid aspiration at Rabin Medical Center from 1999 to 2000 were reviewed for a diagnosis of follicular lesion that warranted surgery (N = 58). The cytology and pathology reports of the patients who met these criteria were reviewed and compared with the original reports., Results: The incidence of malignancy in follicular lesions of the thyroid is about 26%. There was a significant correlation between a histologic diagnosis of carcinoma and the cytologic findings of nuclear grooves (P =.041), solid arrangement (P =.019), hypercellularity (P =.01), and hypercellularity to colloid amount ratio (P =.016). Nodular size was predictive of malignancy. No correlation was found between patient age or gender and tendency toward malignancy., Conclusions: The combination of cytological characteristics and the size of the nodule aspirate are predictive values of malignancy. We believe that every follicular lesion should be excised to obtain a definitive histological diagnosis based on capsular or vascular invasion.

Background: To determine the prognostic value of thyroid suppression therapy in patients with thyroid carcinoma, we studied the effect of thyroid-stimulating hormone (TSH) on the morphology, proliferation rate, and the T3, T4 production rate of primary thyroid carcinoma cells in culture., Methods: From August 1997 to February 1998 tissues were collected for immediate culture from 13 patients undergoing surgery for thyroid cancer. Cells were incubated for 48 h with TSH in different concentrations. T3 and T4 production was measured by radioimmunoassay; cell proliferation was measured in a radioactive counter. Morphology was determined by cytologic examination., Results: Ten samples were eligible for analysis. Changes in TSH affected T3 and T4 levels. The proliferation rate was not influenced by TSH levels., Conclusions: Thyroid papillary carcinoma cells grown in culture maintain their T3 and T4 synthesis ability. This ability is TSH-dependent and correlates with TSH concentration. The morphology of the cells is also maintained. However, their proliferation is not TSH-dependent, placing the current postthyroidectomy treatment policy in question., (Copyright 2001 John Wiley & Sons, Inc.)

A key criterion in the diagnosis of thyroid follicular carcinoma is capsular invasion, but invasion cannot always be demonstrated histologically. Since invasion is likely to evoke reactions in the capsular collagen, we examined the effects of invasion on capsular collagen with the picrosirius orange-red (PSR) staining technique for collagen. Under polarized light, the color of PSR-stained collagen varies as a function of the structural and biochemical properties of the collagen fibers. Capsules of widely invasive carcinomas (n = 10), minimally invasive carcinomas (n = 10), and adenomas (n = 28) were stained with the PSR method. Carcinomas were assessed along the thickened capsule for sites of definite invasion, minimal invasion, and no evidence of invasion. In adenomas, sites of thickened capsules (similar to carcinomas) were compared to sites of thin capsules. All foci were evaluated for the color and color intensity of collagen fibers. We found a significantly higher frequency of yellow-green collagen fibers than of orange-red fibers at sites of invasion, whereas orange-red fibers significantly predominated at non-invaded sites. In a minority of cases both colors occurred but the non-dominant color was of lesser intensity in all but 1 case. There were no significant differences in staining between minimally and widely invasive carcinomas. Thick capsules of adenomas consistently stained with an intense orange-red color, although weakly stained yellow-green fibers were also observed in some of these cases. We conclude that PSR staining can provide diagnostically useful information in capsular samples of carcinomas, when both color and color intensity of PSR staining are evaluated at the same site. Specifically, intense yellow-green birefringence of collagen in a thickened capsule is additional evidence for capsular invasion.

Objective: To evaluate DNA ploidy in papillary thyroid carcinoma in children in correlation to the clinical course of the disease., Methods: Flow cytometric DNA ploidy measurements were performed on formalin-fixed, paraffin-embedded tumor specimens from 14 children and 14 adult patients with papillary carcinoma of the thyroid gland. Analysis of DNA content was performed blind to patient's age and clinical presentation., Results: Seven patients presented with cervical metastasis, one patient had distal metastasis and four patients had local invasion. All patients underwent total thyroidectomy. Seven children underwent bilateral modified neck dissection. Twenty-five tumors expressed diploid DNA content. No statistically significant difference in DNA content was observed between the tumors from child and adult patients. No correlation was found between DNA content and aggressive presentation in the pediatric group., Conclusion: Our primary results indicate that diploid DNA content is common in papillary thyroid carcinoma in children and aggressive clinical presentation is not associated with DNA aneuploidy. Larger prospective studies and long-term clinical follow-up is warranted to document the clinical significance of these observations.

The nuclear parameters of the small lymphocytes in nine cases of small cell lymphomas of the thyroid gland and 17 cases of Hashimoto's thyroiditis were assessed by computer-assisted image analysis. The nuclear area, maximal, minimal and averaged Ferret diameters, perimeter, regularity factor and elongation factor were gauged. Statistically, the nuclear area was ascertained to be the optimum descriptor discriminating between small neoplastic and reactive lymphocytes. Application of a novel variable, combining a nuclear area cut-off value of 14 microm2 with a nuclear averaged Ferret diameter cut-off value of 4.5 micron, allows for the distinction - with a high degree of sensitivity and specificity - between small neoplastic lymphocytes in thyroidal lymphomas and the reactive lymphocytes in Hashimoto's thyroiditis.

Background: Thyroid carcinoma in young patients under the age of 20 years is uncommon. Because of the slow progression of this disease, there is still a great deal of debate as to which operation strategy is best., Methods: We undertook a retrospective study of 61 patients under 20 years of age with thyroid cancer treated at our institute between 1952 and 1995. They constitute 6.6% of the 921 thyroid cancer patients treated by us during the same period. Factors examined were: symptoms, metastases, treatment, complications, and survival., Results: Total or near-total thyroidectomy was performed in 51 patients. Regional lymph node dissection was performed in 17 patients and modified radical neck dissection in 13. Fifty-one patients underwent pretracheal and paratracheal lymph node dissection. During the 43 years of this study, two patients died of thyroid cancer., Conclusions: Although most children are initially seen with more extensive disease than adults, the overall prognosis is excellent. The excellent prognosis is the product of initial aggressive treatment: near-total or total thyroidectomy and at least pre- and paratracheal lymph node dissection, followed by radioactive iodine therapy.

Thyroid cancer is a rare but intriguing malignancy when it occurs in childhood and adolescence. In this retrospective study 58 young patients with thyroid cancer treated at the Rabin Medical Centre are presented. We found that thyroid carcinoma in children presented in a more advanced stage than in adults, and the incidence of regional metastases at the time of presentation is higher. Nevertheless, the biological behaviour of the tumour is more benign. We believe that near-total thyroidectomy is the treatment of choice in this age group for disease limited to the gland, and total thyroidectomy with perithyroidal neck dissection should be performed in patients with nodal disease. For follow-up, we recommend physical examination with measurement of thyroglobulin and TSH levels, ultrasound examination of the neck and chest radiography.

Thyroid cancer is the third most common solid tumor in children and adolescents. A review was made of the data on 540 such patients reported from nine large centers renowned for their experience with thyroid cancer. In respect to the pathogenesis the only factor conclusively known to promote development of thyroid cancer in the pediatric age group is irradiation, as documented by the Chernobyl experience. The evidence indicates that thyroid carcinoma in the pediatric age group is a biologically independent and more aggressive entity than in adults; paradoxically the prognosis is good. In the great majority of cases the only presenting sign was a neck mass. In a high percentage (60-80%) there were also palpable lymph nodes. The findings regarding lung metastases were not clear-cut: in most series they were present in about 10%, with a high of 28% in one group and a low of 5% in another group. Papillary carcinoma or the follicular variant of papillary carcinoma were the dominant histologic types, pure follicular carcinoma being found much less frequently than among adults with thyroid cancer. Despite the relatively advanced stage of the disease upon diagnosis, only 13 patients died of the disease, 12 to 33 years postoperatively. Recurrence rates ranged between 10% to 35%, with involvement of the lateral neck, thyroidal bed or distant sites 3 to 33 years after treatment; most failures responded to further surgery or radioactive iodine. There is almost general agreement that surgical intervention should consist of total or near total thyroidectomy despite the high rates of recurrent laryngeal nerve paralysis and hypocalcemia. In regard to neck metastases less than radical surgery has proved during the years to be sufficiently effective. Radioactive iodine, used by all at some stage of management for treatment purposes, should be used prophylactically only after due consideration in view of possible teratogenicity.

Extrathyroidal invasion of papillary carcinoma of the thyroid gland has a very bad prognosis. A retrospective study was performed on 40 specimens from patients with papillary carcinoma of the thyroid gland to find out whether DNA ploidy correlated with aggressive tumor behavior. The nuclear DNA content of 20 locally aggressive papillary thyroid carcinomas was studied by flow cytometry. The results were compared with those of a matched control group of 20 patients with noninvasive papillary tumors. Forty percent of the tumors with spread to extrathyroid tissue were aneuploid, whereas all the tumors without such extension were diploid. This difference was statistically significant (p < 0.003). The data suggest that the differentiation of locally noninvasive and invasive papillary thyroid carcinomas may be potentially possible by nuclear DNA determination.

Between 1991 and 1994, 600 thyroidectomies were performed at the Beilinson Medical Center in Israel, 120 of which were due to malignancies. Routine preoperative and follow-up ultrasound examinations were performed in 100 cases. A prospective study comparing preoperative ultrasonic and operative findings revealed that ultrasound offered significant preoperative information that could alter operative decisions. Ultrasound also proved to be a valuable tool in follow-up. Based on ultrasound findings, patients were salvaged at an early stage of recurrent disease.

Purpose: This study presents our experience with 728 patients treated in our department for well-differentiated thyroid carcinoma between 1954-1994., Materials and Methods: The retrospective evaluation of the prognostic implications of the clinical and pathological findings was performed. Age, sex, histological variants, tumor size, and locoregional and distant spread were evaluated as risk factors in relation to the prognosis., Results: During follow-up, which ranged from 1 to 31 years, 125 locoregional and/or distant metastases developed (17.2% of the patients), 87 of which occurred in the first 10 years after initial therapy. Thirty-two patients with papillary cancer and 20 with follicular cancer died of causes related to malignancy of the thyroid., Conclusion: The experience gained in our department has led us to adopt an aggressive approach in the treatment of patients with well-differentiated carcinoma of the thyroid gland.

Background: Experimental evidence suggests that tumor growth beyond a certain size and tumor ability to metastasize depend on the degree to which the tumor can stimulate an angiogenic response., Methods: Fifteen thyroid specimens of microinvasive follicular carcinoma were examined for vascularization by immunohistochemical stain with antifactor VIII antibodies and compared with an equal number of follicular adenomas., Results: Pleomorphic areas in the histological specimens of follicular carcinomas had a higher rate of vascularization as did areas of tumor adjacent to or penetrating the capsule. These features were not noted in follicular adenomas., Conclusions: Our findings indicate that vascularity may play a role in extracapsular extension and tumor aggression in follicular thyroid carcinomas.

Thyrocyte HLA-DR expression in association with lymphocytic infiltration has been demonstrated in autoimmune diseases of the thyroid. HLA-DR expression has been noted both in association with lymphocytic infiltration and in its absence. However, no prognostic significance was attributed to these findings. The purpose of this study on papillary carcinoma of the thyroid was to examine how tumour behaviour relates independently to HLA-DR expression and lymphocytic infiltration. Fifty patients with papillary carcinoma with known metastatic status were examined for HLA-DR expression utilizing the immunoperoxidase conjugated indirect method. The patients were divided into three groups: no metastases (n = 16), regional lymph node metastases only (n = 25), and distant haematogenous metastases (n = 9). Overall HLA-DR expression was noted in 6, 36 and 55% of the respective groups. Tumour HLA-DR expression without lymphocytic infiltration was noted in 0, 4 and 33% of the respective groups. Tumour HLA-DR expression with lymphocytic infiltration occurred in 6, 32 and 22% of the respective groups. From these findings we conclude that HLA-DR expression with lymphocytic infiltration occurs more frequently than HLA-DR expression in the absence of infiltration. The concurrence of HLA-DR expression and lymphocytic infiltration is most commonly associated with regional lymph node metastasis. HLA-DR expression in the absence of lymphocytic infiltration occurs in tumours with distant haematogenous metastases and is an uncommon feature of tumours that have not metastasized or have metastasized only to lymph nodes. Tumour HLA-DR expression in the absence of lymphocytic infiltration may indicate the potential for more aggressive behaviour.

Tall cell carcinoma of the thyroid gland is an aggressive variant of papillary carcinoma. A high nuclear DNA content has been associated with aggressive clinical behavior and an unfavorable prognosis in several malignant human tumors. It was also described in differentiated thyroid carcinoma. Therefore, analysis of the nuclear DNA content may yield information predictive of aggressive behavior. Accordingly, the DNA content of the tall cell variant was measured and compared with that of the usual form of papillary carcinoma by flow cytometry. Although all the aneuploid tumors were in the tall cell variant group, the difference in nuclear content was not statistically significant. We conclude that differences in the clinical behavior of these neoplasms are not related to alterations in DNA ploidy.

Between 1954 and 1993 503 patients with papillary carcinoma of the thyroid were treated at the Department of Otolaryngology-Head and Neck Surgery of the Beilinson Medical Center. Two thirds of these patients were women. The median follow-up period was 10.3 years. In more than 30% of cases the tumor was discovered because of the presence of an enlarged lymph node and/or invasion to adjacent structures. Total or near-total thyroidectomy was performed in 381 patients. The 48 patients in whom it was necessary to perform a reoperation had a significantly higher complication rate. Multicentricity was found in 65% of those cases in which both thyroid lobes were available for histologic examination. Nineteen patients were found to have a "tail" cell variant, 223 had a pure papillary variant, and 261 a follicular variant. The mortality rate was 6.2% 15 years after initial therapy. A number of factors-age, size of tumor, presence of distant metastases, "tall" cell variant, and type of surgery-were found to be significant predictors of survival. After almost 40 years of experience in treating more than 500 cases of papillary cancer, we have come to the conclusion that the surgical approach should be aggressive.

A case of metastatic papillary carcinoma of the thyroid is described in which internal jugular vein thrombosis was the initial sign. Local factors, such as compression and invasion, were excluded as causes. A hypercoagulable state associated with deep vein thrombosis is known to accompany some types of adenocarcinomas or autoimmune diseases. We propose that carcinoma-induced hypercoagulability was the course of thrombogenesis in our patient. This is to the best of our knowledge the first report of an association between adenocarcinoma of the thyroid and a hypercoagulable state.

Background: Follicular carcinomas of the thyroid are less common than papillary carcinomas of the thyroid, and the available data on prognostic factors are relatively scant. A retrospective study covering four decades was undertaken to evaluate clinical and pathologic findings with regard to their effect on prognosis., Methods: In 195 cases of follicular carcinoma treated from 1954 to 1991 age, sex, histologic type (minimally invasive vs. widely invasive), tumor size, and local, regional, and distant spread as well as the contribution of treatment to survival were evaluated in relation to prognosis., Results: Age was a significant prognostic factor: there was 100% survival of patients younger than 20 years of age at diagnosis and only one death in the 20-39 year age group. Sex was not a significant prognostic factor, although there was a tendency to a better prognosis in females. Tumor size was significant, more than 6 cm having a poor prognosis. Blood vessel invasion influenced prognosis for the first 10 years. The presence of distant metastases was significant regarding survival. Lymph node involvement had a negative effect on the outcome., Conclusions: The factors of age, tumor size, invasion of blood vessels, and distant metastases are significant predictors of survival for patients with follicular carcinoma, whereas sex is not; regional spread needs to be evaluated further.

Unlabelled: Because of the limitations of periodic 131I whole-body scans, including suspension of substitution therapy, questionable sensitivity and low yield in detecting metastases in patients who have undergone thyroidectomy, serum thyroglobulin and 131I whole-body scans were evaluated for sensitivity in detecting local, regional or distant metastases in 261 patients with differentiated thyroid carcinoma after total thyroidectomy and ablation., Methods: A noncompetitive immunoradiometric assay was used for serum thyroglobulin determination. An 131I whole-body scan was obtained after replacement therapy had been suspended for 6 wk or when TSH reached levels higher than 50 microU/ml. In patients who underwent radiological procedures with iodinated contrast media, the waiting period before the 131I whole-body scan was no less than 10 wk., Results: Of the 58 patients with proven metastases who were followed for 12 yr (mean 7 +/- 3.3 yr), 51 (88.4%) had high serum thyroglobulin assays performed while under full replacement therapy and 32 (55%) showed clear 131I whole-body scan localization. There were no instances of positive whole-body scans and negative serum thyroglobulin., Conclusion: In patients treated with 131I, serum thyroglobulin assay was an excellent method to assess treatment. Patients with metastatic disease and negative whole-body scans with or without serum thyroglobulin exhibited a trend toward higher mortality. This trend may also indicate that the lack of 131I trapping and low thyroglobulin is a sign of metabolic dedifferentiation of otherwise histologically differentiated thyroid tumors.