National Cancer Institute®
Last Modified: April 1, 2002
UI - 11405089
AU - Dotzenrath C; Goretzki PE; Cupisti K; Simon D; Witte J; Yang Q; Ohmann
TI - C; Roher HD Is there any consensus in diagnostic and operative strategy with respect to medullary thyroid cancer? A questionnaire answered by 73 endocrine surgical units.
SO - Langenbecks Arch Surg 2001 Feb;386(1):47-52
AD - St. Antonius Kliniken, Marienheim, Hardtstr. 46, D-42107 Wuppertal, Germany. Dotzenr@uni-duesseldorf.de
BACKGROUND: The purpose of this investigation was to analyze the individual diagnostic and operative strategy in the treatment of medullary thyroid carcinoma (MTC) in international specialized centers and to assess whether standard procedures are carried out in practice everywhere. METHODS: A questionnaire concerning diagnosis and treatment of patients with primary, persistent, or recurrent sporadic or familial MTC was sent to 263 members of the International Association of Endocrine Surgeons. RESULTS: Primary treatment of MTC does not show significant differences for patients with sporadic or familial disease (Chi-square, n.s.), and standard procedures are performed in only 25-40% of patients. Computed tomography scan is the most common localization procedure in persistent or recurrent disease (52-72%), followed by scintigraphy (43-71%), ultrasonography (41-56%), and magnetic resonance imaging (31-49%). In case of negative localization studies, 68-86% of colleagues do not recommend reoperation. In symptomatic patients with stage-IV tumors, however, 84% of colleagues advocate reoperation to provide relief from the tumor burden. CONCLUSIONS: Even with experienced endocrine surgeons, a consensus to uni- and/or bilateral neck dissection in primary MTC is lacking. The majority of authors supports at least total thyroidectomy with central lymph-node dissection. In recurrent disease, there is a general tendency to reoperate in case of positive localization studies and in case of symptomatic disease.
UI - 11454041
AU - Mai KT; Landry DC; Thomas J; Burns BF; Commons AS; Yazdi HM; Odell PF
TI - Follicular adenoma with papillary architecture: a lesion mimicking papillary thyroid carcinoma.
SO - Histopathology 2001 Jul;39(1):25-32
AD - Division of Anatomical Pathology, Department of Laboratory Medicine, The Ottawa Hospital, Ontario, Canada. email@example.com
AIMS: The purpose of this study was to investigate the significance of 'benign' encapsulated follicular thyroid nodules with papillary structures. METHODS AND RESULTS: Twenty-one cases of encapsulated neoplastic thyroid nodules with papillary structures and nuclear features not diagnostic of papillary thyroid carcinoma (PTC) were obtained. All cases were reviewed with particular attention to nuclear features (fine chromatin pattern, optical clearing, grooves and inclusions). Representative sections were submitted for measurement of the maximum diameter of 200 round or nearly round nuclei and for immunostaining for MIB1, CK19, HBME and Ret oncogene protein. Nine cases displayed scattered optically clear nuclei or nuclear grooves in less than 30% of total neoplastic cells. They were grouped in the category of thyroid nodules with limited nuclear features of papillary thyroid carcinoma (PTC), but not diagnostic of PTC. The other 12 cases had fine or coarse chromatin, but lacked other features of nuclei in PTC. The diameter of the nuclei ranged from 5.6 to 7.2 microm and were smaller than those of PTC (6.3-10.0 microm). Immunostaining revealed positive reactivity for MIB1 in the papillary structures. Immunostaining for CK19 and HBME varied from negative or focally weak to diffusely moderate reactivity. Ret oncogene protein immunostaining showed focal and weak reactivity in one case and was negative in other cases of the study. Clinical follow-up from 6 months to 15 years revealed no evidence of metastasis. CONCLUSIONS: The papillary structures in the study cases are unlikely to represent degenerative changes due to their proliferative activity. In view of (i) the encapsulation and the uniformity of the constituent cells, (ii) the varying degrees of immunoreactivity for CK19 and HBME and negative immunoreactivity for Ret oncogene protein, and (iii) the absence or insufficiency of nuclear criteria for the diagnosis of PTC and the absence of lymph node metastasis in all study cases, we believe that these lesions represent the papillary variant of follicular adenoma. Recognition of this pathological entity is important to avoid an over-diagnosis of PTC.
UI - 11737313
AU - Stephenson TJ
TI - Papillary carcinoma of the thyroid: a tumour still with no benign neoplastic counterpart.
SO - Histopathology 2001 Nov;39(5):536-8
AD - Department of Histopathology, Sheffield Teaching Hospitals, Sheffield, UK. firstname.lastname@example.org
UI - 11484280
AU - Velkov M; Mendizov I; Dashev G
TI - [Recurrent nodular goiter. Characteristic features and surgical management]
SO - Khirurgiia (Sofiia) 2000;56(2):17-9
Purpose of the study was to investigate the frequency of the thyroid carcinoma in the recurrent nodular goiter, to analyse the applied operative methods, the observed complications and the obtained early and distant postoperative results. For the period 1985-1996 in the Clinic of Endocrine Surgery were performed 588 reoperations by 577 patients with nodular recurrent goiter, distributed as following: 539 females, aged 14-81 and 49 males, aged 11-69. In 431 cases (73%) was applied medial approach and in 157 cases (27%)--lateral operative approach by the mobilizing of the thyroid recurrence. In the early postoperative period were established the following complications: clinical hypoparathyroidism in 10 patients (1.7%) with calcium level from 1.44-2.01 mmol/l and recurrent nerve paralysis in 28 patients (4.76%), including: in 13 cases unilateral paralysis on the right side, in 9 cases unilateral--on the left side and in 6 cases--bilateral paralysis. The established in 28 patients (4.76%) thyroid carcinoma and the appeared in 59 cases (10%) new recurrence of the basic thyroid disease supported our tactic for radical operative treatment in all patients with nodular recurrent goiter.
UI - 11783847
AU - Radivoyevitch T; Sachs RK; Nikiforov YE; Nikiforova MN; Little MP
TI - On target cell numbers in radiation-induced H4-RET mediated papillary thyroid cancer.
SO - Radiat Environ Biophys 2001 Sep;40(3):191-7
AD - Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USA. email@example.com
Radiation-induced human papillary thyroid cancer (PTC) is associated with chromosomal inversions that involve the genetic loci H4 and RET on chromosome 10. Recently, experimental data has shown that these loci lie in very close spatial proximity in a high proportion of adult human thyroid cells. Applying the generalized formulation of dual radiation action to this H4-to-RET geometric distance data, we predict here the radiation dose-response of H4-RET induction. The predicted H4-RET dose-response has a linear-to-quadratic transition dose of approximately 7 Gy, suggesting the validity of linear risk extrapolations to very low doses for H4-RET mediated radiation-induced PTC. In conjunction with A-bomb survivor data, the predicted H4-RET dose-response yields estimates of the number of PTC target cells that are of the order of approximately 10(6) to approximately 10(7) cells, i.e. considerably less than the total number of follicular cells in the thyroid gland.
UI - 11900218
AU - Sanso GE; Domene HM; Garcia R; Pusiol E; de M; Roque M; Ring A;
TI - Perinetti H; Elsner B; Iorcansky S; Barontini M Very early detection of RET proto-oncogene mutation is crucial for preventive thyroidectomy in multiple endocrine neoplasia type 2 children: presence of C-cell malignant disease in asymptomatic carriers.
SO - Cancer 2002 Jan 15;94(2):323-30
AD - Centro de Investgaciones Endocrinologicas, Hospital de Ninos R. Gutierrez, Buenos Aires, Argentina.
BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) is an inherited disease caused by germline mutations in the RET proto-oncogene, and is responsible for the development of endocrine neoplasia. Its prognosis is dependent on the appearance and spread of medullary thyroid carcinoma (MTC). Relatives at risk can be identified before clinical or biochemical signs of the disease become evident. METHODS: Twenty-one families with MEN 2 (16 families with MEN 2A and 5 families with MEN 2B) were studied. Peripheral blood DNA was amplified by polymerase chain reaction. DNA sequence or restriction enzyme analysis was performed to detect mutations of RET proto-oncogene exons 10, 11, and 16. Molecular analysis was carried out in all index patients as well as in 98 relatives of MEN 2A patients (60 juveniles, ages 6 months to 21 years, and 38 adults, ages 22 to 81 years) and in 13 relatives (6 juveniles ages 10 to 21 years, and 7 adults ages 41 to 66 years) from MEN 2B families. RESULTS: Molecular studies showed a mutation at codon 634, exon 11 in all MEN 2A patients. All MEN 2B patients showed an ATG to ACG (Met918Thr) mutation. In MEN 2A families, 42 out of 98 relatives were affected. Total thyroidectomy was performed in 18 juvenile carriers ages 17 months to 21 years. Histopathologic studies of the glands revealed parafollicular cell (C-cell) hyperplasia in all of these carriers, medullary thyroid carcinoma in 15 carriers, and only one carrier with lymph node metastases. CONCLUSIONS: The consistent finding of C-cell disease in all the juvenile carriers who underwent preventive thyroidectomy emphasizes the relevance of early screening in children at risk of developing MTC. The presence of MTC in the specimen of prophylactic thyroidectomy from a 17 month old girl highlights the importance of thyroidectomy as soon as the molecular diagnosis is confirmed.
UI - 11886336
AU - Belchetz G; Cheung CC; Freeman J; Rosen IB; Witterick IJ; Asa SL
TI - Hurthle cell tumors: using molecular techniques to define a novel classification system.
SO - Arch Otolaryngol Head Neck Surg 2002 Mar;128(3):237-40
AD - Department of Otolaryngology, Mount Sinai Hospital, 600 University Ave, Suite 401, Toronto, Ontario, Canada M5G 1X5.
BACKGROUND: Since ret/PTC gene rearrangements are specific to papillary thyroid carcinoma (PTC), the diagnosis of Hurthle cell PTC (HCPTC) has recently been expanded to include a subset of Hurthle cell tumors (HCTs) that may lack both papillary architecture and/or classic nuclear features but that harbor a ret/PTC gene rearrangement. We hypothesize that such HCPTCs behave in a fashion analogous to other papillary carcinomas, while Hurthle cell carcinomas (HCCs) behave similarly to follicular carcinomas. EDUCATIONAL OBJECTIVES: At the conclusion of this article, participants should be able to discuss HCTs and to identify HCPTCS using molecular techniques. METHODS: A retrospective chart review was carried out on 56 patients with HCTs. All pathological specimens were analyzed for ret/PTC gene rearrangements. Hurthle cell adenoma (HCA) was defined as an HCT that did not exhibit capsular and/or vascular invasion and that lacked a ret/PTC gene rearrangement when evaluated by immunohistochemical and reverse transcription polymerase chain reaction analysis. An HCC was defined as an HCT with capsular and/or vascular invasion that lacked a ret/PTC gene rearrangement, and an HCPTC was defined as any HCT that harbored a ret/PTC gene rearrangement. RESULTS: The subclassification of the 56 HCTs was as follows: 21 HCAs, 15 HCCs, and 20 HCPTCs. No patients with HCA or HCC were ret/PTC positive. Five of the 6 patients with definite lymph node metastasis were in the HCPTC group, demonstrating that molecular analysis helps to explain biological behavior. CONCLUSIONS: Hurthle cell neoplasms can now be classified using histopathological as well as molecular criteria. It appears that the new subclassification of malignant HCTs into follicular (HCC) and papillary (HCPTC) variants identifies 2 distinct biological groups.
UI - 11886339
AU - Khoo ML; Freeman JL; Witterick IJ; Irish JC; Rotstein LE; Gullane PJ;
TI - Asa SL Underexpression of p27/Kip in thyroid papillary microcarcinomas with gross metastatic disease.
SO - Arch Otolaryngol Head Neck Surg 2002 Mar;128(3):253-7
AD - Department of Pathology, University Health Network, 610 University Ave, Suite 4-302, Toronto, Ontario, Canada M5G 2M9.
OBJECTIVE: Papillary microcarcinomas (PMCs) of the thyroid (measuring less than 1 cm in maximum dimension) are extremely common incidental histologic findings, and most of these tumors are not considered clinically significant. However, rare PMCs behave aggressively and metastasize early, giving rise to clinically significant metastatic disease. We hypothesized that p27 and MIB-1/Ki-67 immunoreactivity would allow us to identify this small subgroup of PMCs that have the potential to behave aggressively. METHODS: We reviewed the histopathology reports of 2000 patients who underwent thyroid surgery at our institution between 1995 and 1999 and identified 22 patients who presented with gross regional metastases from a primary PMC. The primary and metastatic tumors were stained for ret, p53, p27, and MIB-1 using the avidin-biotin-peroxidase complex technique. A control group of 33 nonmetastasizing PMCs was also analyzed. RESULTS: Immunoreactivity for ret, p53, and MIB-1 showed no difference between metastasizing and nonmetastasizing PMCs. In most tumors, ret was present, while p53 immunoreactivity was absent in all tumors. MIB-1 staining was present in a small number of cells in both groups of tumors. Immunoreactivity for p27 was quantitated by the intensity of expression as well as the distribution of positive cells within each tumor. All tumors showed lower p27 expression than normal thyroid tissue. However, metastasizing PMCs demonstrated a significantly lower expression of p27 than nonmetastasizing PMCs (P<.001). CONCLUSION: Our results suggest that p27 immunohistochemical analysis may be a valuable diagnostic tool in predicting aggressive potential in PMCs.
UI - 11886341
AU - Roach JC; Heller KS; Dubner S; Sznyter LA
TI - The value of frozen section examinations in determining the extent of thyroid surgery in patients with indeterminate fine-needle aspiration cytology.
SO - Arch Otolaryngol Head Neck Surg 2002 Mar;128(3):263-7
AD - Long Island Surgical Specialists, PC, 410 Lakeville Rd, Suite 310, Lake Success, NY 11042, USA.
OBJECTIVES: To determine the usefulness of intraoperative frozen section (FS) examinations in establishing the diagnosis of thyroid cancer in patients undergoing thyroidectomy for nodules with indeterminate cytological features and to determine the cost-effectiveness of FS examinations in this situation. DESIGN: Retrospective medical record review. The results of fine-needle aspiration biopsies (FNABs), FS examinations, and final pathologic examinations are compared. A cost-effectiveness analysis of routine FS examinations compared with the cost of additional surgical procedures is performed. SETTING: A private surgical practice in a medical school-affiliated teaching hospital. PATIENTS: The records of all 480 patients undergoing thyroidectomy between January 1, 1998, and September 30, 2000, were reviewed. All 199 patients with a dominant thyroid nodule and FNAB results either highly suggestive of papillary cancer or indeterminate were studied. RESULTS: Of the patients with FNAB results highly suggestive of papillary cancer, 95% had cancer according to the final pathologic examination results. The diagnosis of cancer was made by FS examination results in 67% of these patients. Of the remaining 178 patients whose FNAB result was indeterminate, 64 (36%) had thyroid cancer. Malignancy was diagnosed by FS examination results in 30 (47%) of these patients. If FS examinations had not been performed, these 30 patients would have required a second operation to complete a total thyroidectomy. The cost savings of routine FS examinations in patients with indeterminate FNAB results is 1298 US dollars per patient. CONCLUSIONS: The routine performance of FS examinations in patients with thyroid nodules with indeterminate cytological features is a cost-effective way of avoiding a second surgical procedure if a total thyroidectomy is indicated. In patients with FNAB results highly suggestive of papillary cancer, FS examinations are not useful. In these patients, the definitive operation can be based on the results of the FNAB.
UI - 11889153
AU - Kung AW; Chau MT; Lao TT; Tam SC; Low LC
TI - The effect of pregnancy on thyroid nodule formation.
SO - J Clin Endocrinol Metab 2002 Mar;87(3):1010-4
AD - Department of Medicine, University of Hong Kong, China. firstname.lastname@example.org
Epidemiology data have revealed a higher prevalence of nodular goiters in women than men in both iodine-sufficient and iodine-deficient areas. Increased prevalence of thyroid nodules has also been reported in women with higher gravidity. However, the association between pregnancy and thyroid nodule formation has never been studied. The aim of our study was to evaluate the incidence of thyroid nodules during pregnancy and determine whether pregnancy will induce thyroid nodule formation. Two hundred twenty-one healthy southern Chinese women in the first trimester of their pregnancy were studied prospectively. Thyroid ultrasonography, thyroid function tests, and urinary iodine excretion were measured at first, second, and third trimesters of pregnancy as well as 6 wk and 3 months postpartum. Thyroid nodules (>2 mm in any dimension on ultrasonography) were detected in 34 (15.3%) subjects at first trimester, with 12 (5.4%) subjects having more than one nodule. Eight subjects had clinically palpable nodules. Women with thyroid nodules were older (P < 0.01) and had higher gravidity (P < 0.02) than those women without thyroid nodules. The volume of the single/dominant nodules increased from 60 (14--344) mm(3), median (interquartile range) at first trimester to 65 (26-472) mm(3) at third trimester (P < 0.02). These nodules remained enlarged at 103 (25-461) mm(3) 6 wk postpartum (P < 0.005) and 73 (22-344) mm(3) at 3 months postpartum (P < 0.05). Patients with thyroid nodules had lower serum TSH values (P < 0.03) and higher Tg levels (P < 0.05) throughout pregnancy. Appearance of new nodules was detected in 25 (11.3%) women as pregnancy advanced so that by 3 months postpartum, the incidence of thyroid nodular disease was 24.4% (P < 0.02 vs. first trimester). Compared with those with no detectable nodules throughout pregnancy, subjects with new nodule formation had higher urinary iodine excretion from second trimester onward (P all < 0.05). However, no difference could be detected in their TSH and Tg levels throughout pregnancy. Fine-needle aspiration on nodules greater than 5 mm in any dimension after delivery (n = 21) confirmed the majority having histological features consistent with nodular hyperplasia. No thyroid malignancy was detected. In conclusion, pregnancy is associated with an increase in the size of preexisting thyroid nodules as well as new thyroid nodule formation. This may predispose to multinodular goiter in later life.
UI - 11889172
AU - Bachleitner-Hofmann T; Stift A; Friedl J; Pfragner R; Radelbauer K;
TI - Dubsky P; Schuller G; Benko T; Niederle B; Brostjan C; Jakesz R; Gnant M Stimulation of autologous antitumor T-cell responses against medullary thyroid carcinoma using tumor lysate-pulsed dendritic cells.
SO - J Clin Endocrinol Metab 2002 Mar;87(3):1098-104
AD - Department of Surgery, University of Vienna Medical School, Vienna, Austria 1090.
Dendritic cells (DCs) have attracted wide interest because of their unique capacity to elicit primary and secondary antitumor responses. We have generated autologous tumor lysate-pulsed DCs from three patients with medullary thyroid carcinoma (MTC) and tested them for their ability to stimulate cytotoxic T-cell responses against autologous MTC tumor cells in vitro. The aim of our investigations was to evaluate the potential efficacy of DC-based immunotherapy in patients with MTC. DCs were generated from peripheral blood monocytes using GM-CSF and IL-4 (immature DCs) or GM-CSF, IL-4, and TNFalpha (mature DCs). Our results indicate that mature tumor lysate-pulsed DCs are able to elicit a human leukocyte antigen class I-restricted cytotoxic T-cell response against autologous MTC tumor cells, whereas immature tumor lysate-pulsed DCs do not stimulate significant antitumor activity. We feel that our data may be relevant for future clinical trials of active immunotherapy using tumor lysate-pulsed DCs in patients with MTC who have residual or distant disease after surgical treatment. The fact that mature DCs displayed a substantially higher capacity to stimulate autologous antitumor T-cell responses than immature DCs underlines the importance of a maturation step in immunotherapy protocols based on DCs.
UI - 11889175
AU - Puzianowska-Kuznicka M; Krystyniak A; Madej A; Cheng SY; Nauman J
TI - Functionally impaired TR mutants are present in thyroid papillary cancer.
SO - J Clin Endocrinol Metab 2002 Mar;87(3):1120-8
AD - Department of Endocrinology, Medical Research Center, Polish Academy of Sciences, 02-097 Warsaw, Poland. email@example.com
TRs are transcription factors that regulate cell proliferation, differentiation, and apoptosis. They are cellular homologs of the transcriptionally inactive viral oncogene v-erbA. We tested the hypothesis that the functions of TRs could be impaired in cancer tissues as a result of aberrant expression and/or somatic mutations. As a model system, we selected human thyroid papillary cancer, in which the most common abnormalities, RET/papillary thyroid cancer rearrangements (fusion of RET kinase domain to the activating domains of other genes), were found in 40--45% of cases. We found that the mean expression levels of TR beta mRNA and TR alpha mRNA were significantly lower, whereas the protein levels of TR beta 1 and TR alpha 1 were higher in cancer tissues than in healthy thyroid. Sequencing of TR beta 1 and TR alpha 1 cDNAs, cloned from 16 papillary cancers, revealed that mutations affected receptor amino acid sequences in 93.75% and 62.5% of cases, respectively. In contrast, no mutations were found in healthy thyroid controls, and only 11.11% and 22.22% of thyroid adenomas had such TR beta 1 or TR alpha 1 mutations, respectively. The majority of the mutated TRs lost their trans-activation function and exhibited dominant negative activity. These findings suggest a possible role for mutated thyroid hormone receptors in the tumorigenesis of human papillary thyroid carcinoma.
UI - 11889192
AU - Shih A; Davis FB; Lin HY; Davis PJ
TI - Resveratrol induces apoptosis in thyroid cancer cell lines via a MAPK- and p53-dependent mechanism.
SO - J Clin Endocrinol Metab 2002 Mar;87(3):1223-32
AD - Medical Research Service, Stratton Veterans Affairs Medical Center, Albany, New York 12208, USA.
Two papillary thyroid carcinoma (PTC) and two follicular thyroid carcinoma (FTC) cell lines treated with resveratrol (RV), 1-10 microM, showed activation and nuclear translocation of MAPK (extracellular signal-regulated kinase 1/2). Cellular abundance of the oncogene suppressor protein p53, serine phosphorylation of p53, and abundance of c-fos, c-jun, and p21 mRNAs were also increased by RV. Inhibition of the MAPK pathway by either H-ras antisense transfection or PD 98059, an MAPK kinase inhibitor, blocked these RV-induced effects. Addition of pifithrin-alpha, a specific inhibitor of p53, or transfection of p53 antisense oligonucleotides caused decreased RV-induced p53 and p21 expression in PTC and FTC cells. Studies of nucleosome levels estimated by ELISA and of DNA fragmentation showed that RV induced apoptosis in both papillary and follicular thyroid cancer cell lines; these effects were inhibited by pifithrin-alpha and by p53 antisense oligonucleotide transfection. PD 98059 and H-ras antisense transfection also blocked induction of apoptosis by RV. Thus, RV acts via a Ras-MAPK kinase-MAPK signal transduction pathway to increase p53 expression, serine phosphorylation of p53, and p53-dependent apoptosis in PTC and FTC cell lines.
UI - 11889211
AU - D'Elia AV; Tell G; Russo D; Arturi F; Puglisi F; Manfioletti G; Gattei
TI - V; Mack DL; Cataldi P; Filetti S; Di Loreto C; Damante G Expression and localization of the homeodomain-containing protein HEX in human thyroid tumors.
SO - J Clin Endocrinol Metab 2002 Mar;87(3):1376-83
AD - Dipartimento di Scienze e Tecnologie Biomediche, Universita di Udine, 33100 Udine, Italy.
Homeobox genes are involved in neoplastic transformation of both epithelial and hemopoietic tissues. The divergent homeobox gene HEX is expressed in the anterior visceral endoderm during early mouse development and in some adult tissues of endodermal origin, including liver and thyroid. Whereas a role in leukemyogenesis has been proposed already, few data are available on the involvement of HEX in human epithelial tumors. Herein, we analyzed HEX expression and subcellular localization in a series of 55 human thyroid tumors and in several tumoral cell lines. HEX mRNA was detected by RT-PCR either in normal tissues or in thyroid adenomas and differentiated (papillary and follicular) carcinomas. HEX mRNA was also expressed in most undifferentiated carcinomas. Subcellular localization of HEX protein was investigated by immunohistochemistry. In normal tissues and adenomas, HEX protein was present both in nucleus and cytoplasm. In contrast, both differentiated and undifferentiated carcinomas, as well as the tumoral cell lines investigated, showed HEX protein only in the cytoplasm. These findings suggest that regulation of HEX entry in the nucleus of thyrocytes may represent a critical step during human thyroid tumorigenesis.
UI - 11762820
AU - Freyer G; Ligneau B; Schlumberger M; Blandy C; Contedevolx B;
TI - Trillet-Lenoir V; Lenoir GM; Chau N; Dazord A Quality of life in patients at risk of medullary thyroid carcinoma and followed by a comprehensive medical network: trends for future evaluations.
SO - Ann Oncol 2001 Oct;12(10):1461-5
AD - Medical Oncology Unit, Centre Hospitalier Lyon-Sud, and EA 643, Universite Lyon I, France. Gilles.Freyer@chu-lyon.fr
BACKGROUND: As shown in a previous study, the knowledge of the genetic risk in individuals belonging to families at risk of medullary-thyroid carcinoma (MTC) could be associated with impaired quality of life (QoL). PATIENTS AND METHODS: In the present study, we compared the QoL scores obtained in the same period with the subjective quality of life profile (SQLP): in 82 individuals at risk of MTC who had been tested for Ret-mutations; in 200 women at risk of familial breast/ovarian cancer syndrome (BOC); and in a control population of 3,501 healthy volunteers. RESULTS: Significant differences were observed in favour of healthy volunteers as well as individuals at risk of MTC, over women at risk of BOC (mean scores: 0.89, 0.85, and 0.64, respectively, P < or = 0.001), but QoL scores were not statistically different between individuals at risk of MTC and the control population (P = 0.2). However, they were significantly inferior in the subgroup of germline Ret-mutation carriers, as compared to the control population (mean scores: 0.73 and 0.89, P = 0.04). In the latter, the relationships with the children and the family were the most important facets of their QoL. CONCLUSION: Our results confirm the potentially negative impact of the knowledge of the genetic risk of cancer and its consequences in terms of morbidity and follow-up, on the QoL in people followed at oncogenetic visits.
UI - 11881248
AU - Sokolowski E
TI - [Consequences of the Chernobyl accident are difficult to prove. Thyroid gland cancer among those who were exposed to radiation during childhood is the only disease evidently connected to the radiation so far]
SO - Lakartidningen 2002 Jan 31;99(5):418-20
UI - 11888879
AU - Stojadinovic A; Hoos A; Ghossein RA; Urist MJ; Leung DH; Spiro RH; Shah
TI - JP; Brennan MF; Singh B; Shaha AR Hurthle cell carcinoma: a 60-year experience.
SO - Ann Surg Oncol 2002 Mar;9(2):197-203
AD - Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
BACKGROUND: The aim of this study was to define the clinical behavior and prognostic indicators of outcome in Hurthle cell cancer (HCC). METHODS: Diagnosis was confirmed for 56 patients with HCC treated between 1940 and 2000, who form the basis of this study. Primary end points were relapse-free survival (RFS) and disease-specific survival (DSS). Data were analyzed with the Kaplan-Meier method and by log-rank test. RESULTS: The extent of thyroid resection did not predict outcome. Recurrence was a significant predictor of tumor-related mortality. Significant adverse predictors of RFS and DSS were degree of invasion, size >4 cm, extrathyroidal extension, and initial nodal or distant metastases. The most significant predictor of outcome was extent of invasion. Eight-year RFS values for low- and high-risk groups were 100% and 24%. Corresponding rates of 8-year DSS were 100% and 58%. CONCLUSIONS: Widely invasive HCC is an aggressive malignancy that identifies patients who are at high risk for recurrence and tumor-related death. Patients with HCC have a prognosis that is reliably predicted by degree of invasion, tumor size, extrathyroidal disease extension, and initial nodal or distant metastasis. Recurrence portends a poor outcome. High-risk patients and those with recurrence should be considered for adjuvant therapy.
UI - 11832639
AU - Mishra A; Mishra SK
TI - Thyroid nodules in Graves' disease: implications in an endemically iodine deficient area.
SO - J Postgrad Med 2001 Oct-Dec;47(4):244-7
AD - Department of Endocrine Surgery, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow - 226 014, India.
BACKGROUND AND AIM: The presence of thyroid nodules with Graves' disease raises concern about co-existent thyroid malignancy. The objective of this study is to evaluate the risk of thyroid carcinoma and the need for surgical intervention in, patients with Graves' disease with co-existent nodules in an endemically iodine deficient area (IDA). SUBJECTS AND METHODS: Retrospective study of 130 surgically managed patients of Graves' disease (1990-1999). Out of these 35 (26.9%) cases had palpable nodules. No patient had history of previous head and neck irradiation or radioiodine therapy. The clinico-pathological findings and follow-up of these cases were noted. RESULTS: Mean age of patients with nodules was 40.2 +/- 9.5 years and male to female ratio was 1:2.2. The overall incidence of thyroid carcinoma in Graves' disease was 6.2% (8/130 cases), while the incidence, in cases having nodule with Graves' disease was 17.1% (6/35 cases). The median age of patients with carcinoma was 45 years (5 women and 1 man). Besides laboratory investigations for hyperthyroidism, preoperative investigations included fine needle aspiration cytology (FNAC) and thyroid scintigraphy in 29 and 25 cases respectively. Incidence of malignancy in palpable cold nodules was 20%. FNAC could not predict malignancy with certainty in any of these cases. Five patients had papillary thyroid carcinoma while one had follicular carcinoma. Median tumour diameter was 10 mm. Tumour was multi-centric in two cases while one case had metastases to cervical lymph node. In follow-up (median =5.5 years) one patient died of unrelated cause, while rest are alive with no evidence of disease. CONCLUSIONS: Nodules are frequently associated with Graves' disease in IDA. Incidence of carcinoma is high in palpable cold nodule. We recommend early thyroidectomy in these cases.
UI - 11842375
AU - Harach HR; Sanchez SS; Williams ED
TI - Pathology of the autonomously functioning (hot) thyroid nodule.
SO - Ann Diagn Pathol 2002 Feb;6(1):10-9
AD - Services of Pathology and Surgery, "Dr A. Onativia" Endocrinology and Metabolism Hospital, Salta, Argentina.
We describe the pathologic findings of 73 clinically and scintigraphically confirmed hot nodules. In general, hot nodules from an unselected group primarily treated by surgery were smaller and the sex ratio was closer to equality compared with the ample female predominance in the referral, pre-, and post-prophylaxis groups. Malignancy was observed in six cases (8.2%) (5 follicular, 1 papillary). Of the 67 benign tumors, 48 (71.6%) were adenomas which showed the cytoarchitectural features of hot nodules described previously, and 19 (28.3%) were less well-differentiated adenomas that included a few oxyphil tumors. Intracolloid oxalate crystals from background thyroid tissue were present in 59 assessable cases (83%) overall, the majority showed more than occasional crystals that had a tendency to increase in number with decreasing morphologic activity of the thyroid epithelium. Thyroglobulin protein and mRNA stainings tended to be more pronounced in cell cytoplasm of the tumors than in background thyroid. This study shows that hot nodules may show a wide morphologic spectrum of follicular neoplasms and can be occasionally malignant. It is inferred from the morphologic and other findings that it is likely that some, if not all, of the primary follicular cancers associated with hyperfunction arise by clonal progression from benign hot nodules. This progression is rare, probably because most hot nodules present with the symptoms of hyperfunction and receive early treatment. Copyright 2002 by W.B. Saunders Company
UI - 11891946
AU - Absher KJ; Truong LD; Khurana KK; Ramzy I
TI - Parathyroid cytology: avoiding diagnostic pitfalls.
SO - Head Neck 2002 Feb;24(2):157-64
AD - Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. firstname.lastname@example.org
BACKGROUND: Interpretation of parathyroid fine-needle aspirates (FNA) remains problematic not only because this type of specimen is rare but also because the pertinent literature is very limited. We systematically reviewed parathyroid FNAs in our files and sought to delineate additional diagnostic criteria. DESIGN: Review of all thyroid and parathyroid lesions. The final diagnoses included four parathyroid adenomas, one intrathyroidal hyperplastic parathyroid, one intrathyroidal parathyroid adenoma, one atypical parathyroid adenoma (all confirmed by histologic screening or immunocytochemistry), and five parathyroid cysts (all confirmed by immunoassay). Papanicolaou and Diff Quik-stained smears of the parathyroid FNAs were reviewed. The cytologic features were compared and contrasted with those of thyroid FNAs to establish criteria for differential diagnoses. RESULTS: The FNAs of the five parathyroid cysts yielded virtually acellular fluid with a characteristic water-clear appearance and markedly elevated levels of parathyroid hormone. The remaining seven aspirates consisted of moderately cellular smears that showed an admixture of architectural features. Common patterns included cohesive three-dimensional groups, disorganized sheets, papillary fragments, microfollicles, and a single case showing lymphoidlike smears. Although the cells were generally small and round to oval, all cases demonstrated mild to moderate anisokaryosis. The nuclei were hyperchromatic E with coarsely granular chromatin reminiscent of that of small lymphocytes. Occasional nucleoli were noted. Although the cytoplasm was usually pale blue and finely granular with ill-defined borders, two cases showed well-delineated cytoplasmic membranes. Less common findings included cytoplasmic granulation, vacuolization, and rare oxyphilic cells. Naked nuclei were noted in the background of all of the aspirates to varying degrees. Other background findings included the presence of colloidlike material, macrophages, and lymphocytes. One interesting finding that to date has not been reported is the presence of nuclear overlapping (100%) and nuclear molding (71%), which is an uncommon finding in thyroid aspirates. CONCLUSIONS: FNAs of the parathyroid can be easily confused with that of the thyroid, not only because of the clinical similarity between these two types of lesions but also because of the overlap in cytomorphologic features of the aspirated cells. Although no one single cytomorphologic feature is diagnostic, a combination of cytologic parameters noted earlier should raise the possibility of a parathyroid lesion. Aspirates of parathyroid cysts show acellular water-clear fluid with elevated parathyroid hormone measurements. Copyright 2002 John Wiley & Sons, Inc.
UI - 11870476
AU - Berczi C; Mezosi E; Galuska L; Varga J; Bajnok L; Lukacs G; Balazs G
TI - Technetium-99m-sestamibi/pertechnetate subtraction scintigraphy vs ultrasonography for preoperative localization in primary hyperparathyroidism.
SO - Eur Radiol 2002 Mar;12(3):605-9
AD - First Department of Surgery, P.O. Box 27, University of Debrecen, Hungary 1, Nagyerdei str. 98, 4012 Debrecen, Hungary. email@example.com
A prospective study was performed to evaluate the efficacy of technetium-99m-sestamibi and technetium-99m-pertechnetate subtraction scanning and US for imaging parathyroid glands in primary hyperparathyroidism. Sixty-three patients were surgically treated for primary hyperparathyroidism (HPT). Preoperative scintigraphy and US were performed in all cases. Bilateral neck exploration was carried out on each patient. Results of radionuclide studies and US were compared with surgical and histological findings. In 57 patients with primary HPT the radionuclide scanning gave true-positive results. Four false-negative and two false-positive scintigrams were obtained. The sensitivity and the positive predictive value (PPV) of scintigraphy were 93 and 97%, respectively. Forty-one cases were correctly localized by the US. Seventeen US results were false negative and five were false positive. The sensitivity and the PPV for US were 71 and 89%, respectively. There was a statistically significant difference between the sensitivity of the scintigraphy compared with the US ( p=0.001). Sensitivities of radionuclide scans and US were higher for adenomas (100 and 83%) than for hyperplastic glands (75 and 40%). The sensitivity of technetium-99m-sestamibi and technetium-99m-pertechnetate subtraction scintigraphy was significantly higher compared with US. This sensitive method could help surgeons in performing a rapid and directed parathyroidectomy.
UI - 11891962
AU - Stoler DL; Datta RV; Charles MA; Block AW; Brenner BM; Sieczka EM; Hicks
TI - WL Jr; Loree TR; Anderson GR Genomic instability measurement in the diagnosis of thyroid neoplasms.
SO - Head Neck 2002 Mar;24(3):290-5
AD - Department of Experimental Pathology, Roswell Park Cancer Institute, Buffalo, New York, USA.
BACKGROUND: Clinically palpable thyroid nodules are present in approximately 10% of the population, although only 5% to 7% of these nodules harbor malignancy. Fine-needle aspiration has become one of the central tools in the diagnostic armamentarium of the surgeon/endocrinologist. There is, however, up to a 30% indeterminate diagnostic rate associated with this technique, resulting in unnecessary surgical interventions for patients harboring benign disease. A second issue of clinical importance is the unreliability of predicting outcomes based either on histologic findings alone or in combination with clinical staging. To address these diagnostic and clinical shortcomings, we have used measurement of genomic instability as a diagnostic and prognostic indicator for thyroid neoplasms. METHODS: Genomic instability of thyroid tissue samples was determined by inter-(simple sequence repeat) PCR, microsatellite instability analysis, and fluorescence in situ hybridization (FISH) on thyroid neoplasms from 22 patients. RESULTS: Inter-(simple sequence repeat) PCR detected genomic instability with an index range 0% to 1.9% (mean, 0.56%) in patients with benign disease, whereas in patients with malignant histologic findings the values ranged from 0% to 6.6% (mean, 2.9%). This difference between benign and malignant values was statistically significant (p =.004). There was no demonstrable microsatellite instability or loss of heterozygosity for six markers examined in this group. Losses of chromosomes 17 and X in benign disease and gains of chromosomes 7, 12, 17, and X in Hurthle cell carcinoma were observed, although not at a significant rate. CONCLUSIONS: Genomic instability as measured by inter-(simple sequence repeat) PCR was significantly higher for malignant diseases compared with benign thyroid tissues, but no such association was seen with aneuploidy or microsatellite instability. Copyright 2002 Wiley Periodicals, Inc.
UI - 11919168
AU - Grimm D; Bauer J; Kossmehl P; Shakibaei M; Schoberger J; Pickenhahn H;
TI - Schulze-Tanzil G; Vetter R; Eilles C; Paul M; Cogoli A Simulated microgravity alters differentiation and increases apoptosis in human follicular thyroid carcinoma cells.
SO - FASEB J 2002 Apr;16(6):604-6
AD - Institute of Clinical Pharmacology and Toxicology, Benjamin Franklin Medical Center, Freie Universitat Berlin, Germany. firstname.lastname@example.org
This study focuses on the effects of simulated microgravity (0g) on the human follicular thyroid carcinoma cell line ML-1. Cultured on a three-dimensional clinostat, ML-1 cells formed three-dimensional MCTSs (MCTS diameter: 0.3 +/- 0.01 mm). After 24 and 48 h of clinorotation, the cells significantly decreased fT3 and fT4 secretion but up-regulated the thyroid-stimulating hormone-receptor expression as well as the production of vimentin, vinculin, and extracellular matrix proteins (collagen I and III, laminin, fibronectin, chondroitin sulfate) compared with controls. Furthermore, ML-1 cells grown on the clinostat showed elevated amounts of the apoptosis-associated Fas protein, of p53, and of bax but showed reduced quantities of bcl-2. In addition, signs of apoptosis became detectable, as assessed by terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick end labeling, 4', 6-diamidino-2-phenylindole staining, DNA laddering, and 85-kDa apoptosis-related cleavage fragments. These fragments resulted from enhanced 116-kDa poly(ADP-ribose)polymerase (PARP) activity and apoptosis. These observations suggest that clinorotation elevates intermediate filaments, cell adhesion molecules, and extracellular matrix proteins and simultaneously induces apoptosis in follicular thyroid cancer cells. In conclusion, our experiments could provide a regulatory basis for the finding that astronauts show low thyroid hormone levels after space flight, which may be explained by the increase of apoptosis in thyrocytes as a result of simulated 0g.
UI - 11799311
AU - Hadjieva T
TI - Scoring patients' risk in differentiated thyroid cancer.
SO - Onkologie 2001 Dec;24(6):561-8
AD - Radiotherapy Department, University Hospital Queen Giovanna, Faculty of Medicine, Sofia, Bulgaria. email@example.com
BACKGROUND: Despite of excellent long-term results, there is a need for the selection of patients with differentiated thyroid cancer who experience an unfavorable outcome. PATIENTS AND METHODS: Between 1980 and 1997, 406 patient