National Cancer Institute®
Last Modified: August 1, 2002
UI - 12094241
AU - Williams D
TI - Cancer after nuclear fallout: lessons from the Chernobyl accident.
SO - Nat Rev Cancer 2002 Jul;2(7):543-9
AD - Thyroid Carcinogenesis Research Group, Strangeways Research Laboratory, Wort's Causeway, Cambridge, CB1 8RN, UK. email@example.com
UI - 12142399
AU - Morris LF; Waxman AD; Braunstein GD
TI - Interlaboratory comparison of thyroglobulin measurements for patients with recurrent or metastatic differentiated thyroid cancer.
SO - Clin Chem 2002 Aug;48(8):1371-2
UI - 12097277
AU - Schagdarsurengin U; Gimm O; Hoang-Vu C; Dralle H; Pfeifer GP; Dammann R
TI - Frequent epigenetic silencing of the CpG island promoter of RASSF1A in thyroid carcinoma.
SO - Cancer Res 2002 Jul 1;62(13):3698-701
AD - AG Tumorgenetik der Medizinischen Fakultat, Martin-Luther-Universitat Halle-Wittenberg, Halle/Saale, Germany.
Loss of heterozygosity of chromosome 3p21 is one of the most frequent alterations in solid tumors, including thyroid carcinomas. Recently, we have characterized the novel tumor suppressor gene RASSF1 located in this locus. The RASSF1A isoform is epigenetically inactivated in a variety of human primary tumors. In this study, we investigated the expression and methylation status of the RASSF1 gene in thyroid carcinoma. In nine thyroid cancer cell lines, the RASSF1A promoter CpG island was methylated completely, and expression was absent. Treatment of these cell lines with the DNA methylation inhibitor 5-aza-2'-deoxycytidine reactivated the transcription of RASSF1A. The methylation status of the RASSF1A promoter was analyzed in 38 primary thyroid tumors, including 1 poorly differentiated thyroid carcinoma, 5 medullary thyroid carcinoma (MTC), 10 follicular thyroid carcinoma (FTC), 9 undifferentiated thyroid carcinoma (UTC), and 13 papillary thyroid carcinoma (PTC). In 71% of thyroid carcinomas, the RASSF1A CpG island was hypermethylated. Methylation frequency was higher in the aggressive forms of thyroid carcinoma and was found in 80% of MTC, in 78% of UTC, and in 70% of FTC, compared with 62% in the more benign PTC. RASSF1A inactivation was detected in all stages of thyroid carcinoma scored by Tumor-Node-Metastasis classification. Additionally, we analyzed the methylation frequency of the CpG island of cell cycle inhibitor p16(INK4a) in the same thyroid tumors. The p16 gene was inactivated in 56 and 25% of cell lines and primary tumors, respectively. p16 methylation was detected in 56% of UTC, 10% of FTC, and 25% of PTC but not in MTC. In UTC, which belongs to the most aggressive carcinomas in humans, the most common combined inactivation of RASSF1A and p16 was detected. In general, 90% of tumors with p16 inactivation were also silenced for RASSF1A expression. However, RASSF1A hypermethylation was detected three times more frequently in thyroid cancers. Thus, RASSF1A inactivation may play a crucial role in the malignancy of thyroid carcinoma.
UI - 12127404
AU - Bauer AJ; Cavalli LR; Rone JD; Francis GL; Burch HB; Tuttle RM; Ringel
TI - MD; Stratakis CA; Haddad BR Evaluation of adult papillary thyroid carcinomas by comparative genomic hybridization and microsatellite instability analysis.
SO - Cancer Genet Cytogenet 2002 Jun;135(2):182-6
AD - Department of Pediatrics, Walter Reed Army Medical Center, USA, Washington, DC, USA.
To clarify the mechanism of tumorigenesis in papillary thyroid carcinoma (PTC) and ascertain whether genomic changes correlate with histologic features, we conducted a comprehensive molecular evaluation of PTC using comparative genomic hybridization (CGH) and microsatellite instability (MSI) analysis in a set of 17 histologically well-characterized PTC specimens. To our knowledge, this is the first study that evaluates chromosomal and nucleotide instability in the same PTC tumor specimens. Four of 15 samples (27%) had aberrations detected by CGH. All four had a partial or complete gain of chromosome 20, and 3 of 4 had a partial or complete loss of chromosome 13. No MSI was detected in any of the PTC samples (n=16), and all samples examined by immunohistochemistry (n=9) expressed the DNA repair enzymes hmlh1 and hmsh2. All PTC samples with abnormal CGH had vascular invasion or invasion of the thyroid capsule, and there was a significant correlation between the presence of chromosomal aberrations and capsular/vascular invasion (P=0.026). We conclude that although chromosomal and microsatellite instability are uncommon in PTC, tumors with chromosomal aberrations are more likely to be associated with invasion.
UI - 11939753
AU - Brenta G; Schnitman M; Bonnahon L; Besuschio S; Zuk C; De Barrio G;
TI - Peruzzotti C; Saubidet G Evaluation of innovative skin-marking technique performed before thyroid ultrasound-guided fine-needle aspiration biopsies.
SO - Endocr Pract 2002 Jan-Feb;8(1):5-9
AD - Department of Endocrinology and Metabolism, Hospital Frances, Buenos Aires, Argentina.
OBJECTIVE: To introduce an innovative skin-marking technique performed before ultrasound-guided fine-needle aspiration biopsy (US-FNAB) of the thyroid. METHODS: We studied 248 patients with thyroid nodules, who were classified on the basis of physical examination into two groups-those with palpable nodules (N = 127) and those with nonpalpable or difficult-to-palpate nodules (N = 121). Each group was further subdivided according to the size of the thyroid nodule (< or = 15 mm versus >15 mm). Before US-FNAB, we performed the skin-marking technique with the aid of a catheter, a permanent marker, and ultrasound guidance. An established point for needle entry was indicated on the skin. The chi-square test was used to compare results between the groups of patients. RESULTS: The proportions of adequate and insufficient biopsy material in the overall group of patients were 88.7% and 11.3%, respectively. When the patients were stratified by palpable and nonpalpable thyroid nodules, biopsy specimens were adequate in 89.8% and insufficient in 10.2% of those with palpable nodules, whereas the corresponding proportions for those with nonpalpable nodules were 87.6% and 12.4%, respectively. No statistically significant differences were noted between the two groups. Comparisons between patients with thyroid nodules >15 mm in their largest diameter versus those with nodules < or =15 mm also showed no statistically significant differences in terms of insufficient biopsy material. CONCLUSION: Our technique creates a marking on the skin that leads directly to the thyroid nodule and facilitates the acquisition of adequate cytologic material. This is particularly relevant when small transducers are not available or when the physician needs reassurance about the accuracy of the thyroid biopsy site.
UI - 12107391
AU - Argalia G; De Bernardis S; Mariani D; Abbattista T; Taccaliti A;
TI - Ricciardelli L; Faragona S; Gusella PM; Giuseppetti GM [Ultrasonographic contrast agent: evaluation of time-intensity curves in the characterisation of solitary thyroid nodules]
SO - Radiol Med (Torino) 2002 Apr;103(4):407-13
AD - Radiologia Clinica, Universita degli Studi, Ancona, Italy.
PURPOSE: To propose a new method for the assessment of the fluidodynamic behaviour of angiographic contrast agents. The method enables measurement of the spatial distribution and time dependence of the contrast agent along a pseudo-vessel on images obtained with an X-ray image intensifier. MATERIAL AND METHODS: A particular phantom was devised consisting of a plexiglas box with an insert into which a latex tube with a 0.4 cm in diameter was placed in order to simulate the tortuous flow of a blood vessel. The box, which is filled with water to simulate the thickness of a normal patient, is connected to an injection and pumping system which serve to keep the contrast agent flowing in the pseudo-vessel tube. The pseudo-vessel tube was filled with plain water in one case and with saline solution in another case to assess their different dilution capabilities. The phantom and the flow of contrast agent were imaged with a conventional X-ray image intensifier system and the images were stored in digital format during 35 second acquisitions at a speed of 4 frames per second; for any frame it is possible to measure the mathematical contrast in any position in the image. Further, a diagram showing the time dependence of the spatial distribution of the mathematical contrast is proposed. The X axis shows the spatial distribution of the mathematical contrast, whereas the Y axis shows its temporal variation with a gray level proportional to the mathematical contrast value. By building an horizontal profile of this diagram one can obtain the spatial distribution at a fixed time, while by building a vertical profile one can obtain the temporal variation at a fixed point. Several different contrast agents were so tested. RESULTS: The proposed method allows different fluido-dynamic behaviour patterns of contrast agents and flowing media to be shown. Owing to the different chemical characteristics of water and saline solution these media have different dilution capabilities (higher for water) and this is well demonstrated by the diagram profiles obtained for each. The system has also allowed the detection of a particular behaviour of some contrast agents, whose spatial distribution was non uniform even in the last frames, thus showing a tendency to maintain their bolus-nature over time. An interesting feature which can be noticed in all the temporal profiles is the presence of a "pre-bolus", i.e. the contrast is higher at the very beginning of the flow, then decreases and after some time starts to increase again. Though the initial contrast value obviously depends on the iodine concentration employed, the method shows the contrast variation as a function of time is different for different contrast agents. CONCLUSIONS: The method and the equipment proposed provide a good description of the fluidodynamic behaviour of different contrast agents, but do not constitute a reference method for testing haemodynamic behaviour which, "in vivo", is obviously affected by several other chemical and metabolic factors. However, the method allows evaluation of the contrast agents from a physical and fluidodynamic point of view, showing that the iodine content is not the only feature affecting their behaviour. The method can be used in quality control to test the constancy of the physical behaviour of different contrast agents.
UI - 11798772
AU - Xu S; Wang P; Yu Z
TI - [Clinical research of Hashimoto's disease with thyroid carcinoma]
SO - Zhonghua Yi Xue Za Zhi 2000 Apr;80(4):278-9
AD - Second Affiliated Hospital, Zhejiang University, Hangzhou 310009, China.
OBJECTIVE: To study the relation diagnosis and treatment of Hashimoto's disease (HD) with thyroid carcinoma (TC). METHODS: The relation diagnosis and surgical treatment of 150 cases of HD including 15 cases of TC were analyzed. RESULTS: The coexistent rate of HD with TC was 10%. The 15 cases were all women, with a mean age of 36.5 years, and they were surgically treated. Follow-up for 4 months to 19 years showed that the 15 cases were alive without recurrence. CONCLUSION: Surgical treatment is indicated for patients with HD associated with TC. The essential factors for diagnosis and rational treatment are a detailed understanding of clinical feature, routine examination of serum antibodies, B-ultrasonic examination and selective FNAC.
UI - 12140869
AU - Lewy-Trenda I
TI - Estrogen and progesterone receptors in neoplastic and non-neoplastic thyroid lesions.
SO - Pol J Pathol 2002;53(2):67-72
AD - Department of Pathomorphology, Medical University, Lodz.
The pathogenesis of thyroid cancer is complex. Iodium deficiency, genetic factors, sex, older age, irradiation in childhood, thyroid growth stimulating antibodies and epithelial growth factor possibly affect its development. Recent reports, also epidemiological, have shown that differentiated thyroid cancer (papillary, follicular, oxyphillic) is dependent on sex hormones, especially estrogens. This has prompted research into the presence of estrogens and progesterone, as well as androgen receptors (ER, PR and AR) in normal and neoplastic thyreocytes and estradiol content in thyroid tissue. The results of these investigations imply that thyroid cancers are estrogen-dependent. There is, however, no agreement in reports about correlation between tumor malignancy and ER, PR and AR expression. In this study 72 thyroid glands have been examined using immunohistochemical assays with ERs and PRs antibodies. Positive staining was demonstrated mainly in differentiated thyroid cancer nuclei (17 ERs positive and 2 PRs positive). There was no expression of antibodies in non-neoplastic cells or in adjacent tissues. The nuclei of 3 oxyphillic and 4 follicular adenomas were also ERs positive. On the other hand nuclei of 5 follicular adenomas were PRs positive. These results are in agreement with most available data. It seems, however, that the material so far examined by the investigators is too small. Furthermore, because of using various methods the results cannot be compared. Further studies are necessary to reveal if there is any true influence of sex hormones on the development of thyroid lesions and if the detection of sex hormone receptors may help in choosing adequate therapy.
UI - 12109616
AU - Livolsi VA
TI - Risk group-based management of differentiated thyroid carcinoma.
SO - J R Coll Surg Edinb 2002 Jun;47(3):589-90; discussion 590
UI - 11956701
AU - Ron E
TI - Ionizing radiation and cancer risk: evidence from epidemiology.
SO - Pediatr Radiol 2002 Apr;32(4):232-7; discussion 242-4
AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 6120 Executive Boulevard, Rockville, MD 20852, USA. firstname.lastname@example.org
UI - 12048627
AU - Koike E; Yamashita H; Noguchi S; Ohshima A; Yamashita H; Watanabe S;
TI - Uchino S; Arita T; Kuroki S; Tanaka M Endoscopic ultrasonography in patients with thyroid cancer: its usefulness and limitations for evaluating esophagopharyngeal invasion.
SO - Endoscopy 2002 Jun;34(6):457-60
AD - Noguchi Thyroid Clinic and Hospital Foundation, Oita, Japan.
BACKGROUND AND STUDY AIMS: Although computed tomography (CT) and magnetic resonance imaging (MRI) are useful for detecting esophagopharyngeal invasion by thyroid cancer, they cannot assess the depth of invasion, which is important for the surgical planning. In the present study, endoscopic ultrasonography (EUS) of the esophagus was used to assess esophagopharyngeal invasion by thyroid cancer, and the value of this technique was assessed prospectively. PATIENTS AND were carried out in 59 patients in whom esophagopharyngeal invasion by thyroid cancer was suspected due to large tumors or tumors with poor mobility. The EUS findings were evaluated in 52 patients (10 men, 42 women; mean age 62.4 years; mean tumor size 39.5mm) with complete resections, and compared with the pathological results. RESULTS: The diagnostic specificity and accuracy of EUS in assessing invasion into the muscularis propria (82.9 %, 82.7 %) were greater than those of MRI (60 %; P = 0.034, 65.4 %; P = 0.044) and esophagography (58.8 %; P = 0.034, 60 %; P = 0.028). The accuracy for detecting cancer invasion located in the upper part of the lobe was less than for invasion in the middle and/or lower parts of the lobe ( P = 0.020). Conclusions. EUS is useful for assessing esophagopharyngeal invasion by thyroid cancer, although its effectiveness may be limited in thyroid lesions located in the upper part of the lobe.
UI - 12142170
AU - Vini L; Harmer C
TI - Management of thyroid cancer.
SO - Lancet Oncol 2002 Jul;3(7):407-14
AD - Department of Clinical Oncology, Athens Medical Center, Greece.
Thyroid cancers are a diverse group of malignant disorders ranging from indolent micropapillary carcinoma, which has no effect on life expectancy, to anaplastic tumours, which are invariably fatal even with aggressive treatment. Although the estimated incidence has increased by 14.6% over the past 40 years, the estimated death rate has fallen by 21%, probably as a result of earlier diagnosis. The natural history of thyroid tumours is no longer a mystery, and the prognostic factors identified can predict outcome fairly accurately. Improvements in management have mostly depended on information from large retrospective series, though there are still many areas open to debate. There has been, however, a general acceptance that thyroid cancer should be managed by multidisciplinary teams in specialised units following evidence-based guidelines.
UI - 12146030
AU - Kim JY; Cho H; Rhee BD; Kim HY
TI - Expression of CD44 and cyclin D1 in fine needle aspiration cytology of papillary thyroid carcinoma.
SO - Acta Cytol 2002 Jul-Aug;46(4):679-83
AD - Departments of Pathology, Internal Medicine and Surgery, Inje University, Sanggye Paik Hospital, Seoul, Korea.
OBJECTIVE: To compare the expression pattern of CD44 and cyclin D1 immunostaining in fine needle aspiration specimens of papillary carcinoma of the thyroid and nonpapillary lesions. STUDY DESIGN: The study was performed on 80 fine needle aspiration cytologic smears of thyroid lesion retrospectively using monoclonal antibodies and on histologic material from a proportion of cases. RESULTS: Most papillary carcinomas expressed intense cell membrane or diffuse cytoplasmic staining for CD44 (97.8%). Focal immunoreactivity was observed in follicular neoplasms (28.5%) and nodular goiter (4.7%). There was no difference in CD44 immunostaining between follicular carcinoma and adenoma. Cyclin D1 was expressed in the nuclei of most papillary carcinomas (79.2%). Focal nuclear immunoreactivity was noted in nodular goiters (23.5%) and follicular neoplasms (10%). In resected specimens, all papillary carcinomas (19 cases) showed intense membranous or granular CD44 immunoreactivity. Focal cyclin D1 expression was noted in 52.6%. There was no difference in CD44 and cyclin D1 expression between the group of papillary carcinomas with regional lymph node metastasis as compared to those without metastasis. Positive staining for both CD44 and cyclin D1 would strongly favor papillary carcinoma, although further studies on cytologic material are necessary to verify this diagnostic approach. CONCLUSION: Most papillary carcinomas express CD44 and cyclin D1, whereas it is less common in follicular neoplasms and nodular goiter. This may be helpful in diagnostically difficult cases.
UI - 12146049
AU - Merchant FH; Hirschowitz SL; Cohan P; Van Herle AJ; Natarajan S
TI - Simultaneous occurrence of medullary and papillary carcinoma of the thyroid gland identified by fine needle aspiration. A case report.
SO - Acta Cytol 2002 Jul-Aug;46(4):762-6
AD - Cytopathology Division, Department of Pathology and Laboratory Medicine, Endocrinology Division, Department of Medicine, University of California-Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095-1732, USA.
BACKGROUND: Fine needle aspiration (FNA) diagnosis of simultaneous medullary and papillary thyroid carcinoma in independent thyroid lobes is exceedingly rare. CASE: A 36-year-old female presented with a one-month history of dysphagia. Thyroid ultrasound revealed a multinodular goiter. She was clinically and biochemically euthyroid. FNA of the right thyroid nodule was consistent with medullary carcinoma, and FNA of the left thyroid lobe was consistent with papillary carcinoma. Immunohistochemistry revealed strong calcitonin and CEA positivity in the right lobe and lack of staining in the left lobe. Conversely, staining for thyroglobulin was negative on the right lobe and positive on the left lobe. CONCLUSION: The patient developed tumors in separate lobes of the thyroid. Immunoreactivity of calcitonin, CEA and thyroglobulin made a sharp distinction between the two tumors. Therefore, we conclude that these tumors were not linked by either embryology or genetics.
UI - 11961499
AU - Cappelli C; Agosti B; Tironi A; Morassi ML; Pelizzari G; Cumetti D;
TI - Cerudelli B [Prevalence and aggressiveness of thyroid carcinoma with diameter less than one centimetre in iodine deficiency areas]
SO - Minerva Endocrinol 2002 Jun;27(2):65-71
AD - Sezione di Endocrinologia, II Medicina, Universita degli Studi, Brescia, Italy.
BACKGROUND: The introduction of highly sensitive imaging techniques has made it possible to detect many non-palpable thyroid nodules with size less than 1 centimetre. The prevalence of these lesions appears to be high in the general population and increases in iodine deficiency areas. Fine needle aspiration biopsy (FNAB) is considered the most reliable 4871 (73.5%) euthyroid patients the mean daily urinary excretion of iodine was 73+/-18 micromg/day. RESULTS: In 2401 nodules (36.2%) the diameter was less than one centimetre. Histologic confirmation of malignancy was available in 187 (89.9%) of 208 operated nodules with diameter more than 1 cm and in 64 (78%) of 82 with diameter less than 1 cm. Logistic regression analysis indicated that a solid hypoechoic feature was a useful criterion to predict malignancy (p<0.001), as well as the presence of calcification (p<0.5) and blurred margins (p<0.5). Lymph node metastases were present in 24.3% of carcinomas with diameter more than 1 cm but, surprisingly, also in 20.3% of those with diameter less than 1 cm. No correlation was seen between diameter of carcinoma nodules and presence of lymph node metastasis. CONCLUSIONS: These data suggest that the potential malignancy of thyroid nodules is not only correlated to the diameter but to other parameters such as the biological difference of thyroid cancer that could be hypothesized in an iodine deficiency area. In conclusion, FNAB is recommended for nodules with diameter less than 1 centimetre when sonographic findings suggest malignancy such as a hypoechoic pattern, an irregular margin or internal microcalcification.
UI - 12087618
AU - Schultz PN
TI - Providing information to patients with a rare cancer: using Internet discussion forums to address the needs of patients with medullary thyroid carcinoma.
SO - Clin J Oncol Nurs 2002 Jul-Aug;6(4):219-22
AD - email@example.com
Medullary thyroid carcinoma (MTC) is a rare disease, and specific experience with the condition is not commonly found outside of major cancer centers. Because of the rarity and slow-growing natural history of the disease, patients with MTC frequently have many questions concerning prognosis, treatment, and follow-up care. Many of these patients have joined an e-mail group on the Internet through which they share information and concerns. The author has joined this group and shares her expert clinical knowledge about the disease. When individuals are armed with accurate and expert information, they can make informed decisions. The source of this information can be diverse. Nurses with expert knowledge can use opportunities such as e-mail groups to answer questions and respond openly about subjects about which they have unique perspectives.
UI - 12119278
AU - Eng C
TI - Role of PTEN, a lipid phosphatase upstream effector of protein kinase B, in epithelial thyroid carcinogenesis.
SO - Ann N Y Acad Sci 2002 Jun;968():213-21
AD - Clinical Cancer Genetics and Human Cancer Genetics Programs, Comprehensive Cancer Center, and Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210, USA. firstname.lastname@example.org
Both benign and malignant thyroid disease are well-established components of Cowden syndrome (CS), an autosomal dominant disorder characterized by multiple hamartomas and breast cancer that may be considered a phakomatosis. The susceptibility gene for CS is PTEN, a tumor suppressor gene on 10q23.3 that encodes a lipid phosphatase that lies upstream of protein kinase B (Akt). Interestingly, Carney complex is also a phakomatosis where multiple endocrine neoplasias are prominent and thyroid cancer might be a rare component. One of its susceptibility genes is the regulatory subunit of protein kinase A. Over the course of the last four years, investigators have found the increasing clinical spectrum of syndromes characterized by germline loss-of-function PTEN mutation. In addition to CS, subsets of such disparate syndromes as Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and possibly VATER with hydrocephalus and megencephaly with autistic features have been found to have germline PTEN mutations. Paradoxically, somatic intragenic PTEN mutations were rare in uncultured primary epithelial thyroid tumors, although hemizygous deletion occurred in 10-20% of thyroid adenomas and carcinomas. However, with subsequent study, it was discovered that epigenetic silencing of PTEN and perhaps inappropriate subcellular compartmentalization were two novel mechanisms of PTEN inactivation pertinent in thyroid carcinogenesis. Ectopic expression studies in vitro have borne out the importance of PTEN in the pathogenesis of epithelial thyroid neoplasias.
UI - 12146987
AU - Lee NC; Norton JA
TI - Multiple-gland disease in primary hyperparathyroidism: a function of operative approach?
SO - Arch Surg 2002 Aug;137(8):896-9; discussion 899-900
AD - Department of Surgery, University of California, San Francisco, USA.
HYPOTHESIS: The approach to surgery for primary hyperparathyroidism (PHPT) is controversial. To determine whether routine bilateral neck exploration increases the detection of multiple-gland disease compared with a focused unilateral approach, we compared the incidence of single vs multiple-gland disease in patients undergoing surgical treatment for PHPT as a function of unilateral or bilateral exploration. DATA SOURCES: From 1993 through 1997, 214 consecutive patients underwent initial bilateral neck exploration for PHPT by a single surgeon. Each patient underwent the surgical procedure without prior localizing studies. Four parathyroid glands were identified, and abnormal glands were excised. The results were compared with published studies of patients who underwent either bilateral neck exploration or focused unilateral neck exploration for PHPT. STUDY SELECTION: All reported studies from 1995 through 2001 in a MEDLINE search using the terms "parathyroidectomy" or "primary hyperparathyroidism and surgery" and either "bilateral" or "conventional" or "minimally invasive," "selective," or "unilateral." DATA EXTRACTION: The studies were analyzed for numbers of patients and a final diagnosis of either a single adenoma or multiple-gland disease (double adenoma or hyperplasia). Proportions were compared statistically with a chi(2) test. DATA SYNTHESIS: In our series of 214 patients who underwent bilateral neck exploration, 79.4% had a single adenoma, and 20.6% had multiple-gland disease. Of 2166 patients in 14 studies who underwent bilateral neck exploration, 79.7% had a single adenoma, and 19.3% had multiple-gland disease. Of 2095 patients in 31 studies with a focused unilateral approach, 92.5% had a single adenoma, whereas only 5.3% had multiple-gland disease. The incidence of multiple-gland disease was significantly lower among patients treated with a focused unilateral approach compared with a bilateral approach as used in our series and the literature (P<.001). CONCLUSION: The data suggest that a focused unilateral surgical approach for PHPT may underestimate the incidence of multiple-gland disease.
UI - 12162676
AU - Cerilli LA; Mills SE; Rumpel CA; Dudley TH; Moskaluk CA
TI - Interpretation of RET immunostaining in follicular lesions of the thyroid.
SO - Am J Clin Pathol 2002 Aug;118(2):186-93
AD - Robert E Fechner Laboratory of Surgical Pathology, University of Virginia Health Sciences Center, Charlottesville, USA.
We applied monoclonal antibodies against RET and cytokeratin 19 (CK19) to the following tumor sections: classic papillary carcinoma (PC), 16; Hurthle-type PC (HPC), 1; sclerosing PC with nodular fasciitis-like stroma (SPC), 1; PC, follicular variant (FVPC), 12; follicular adenoma (FA), 9; Hurthle cell adenoma (HA), 4; Hurthle cell carcinoma (HC), 3; and follicular carcinoma (FC), 7. CK19+ tumors included 16 PCs, 1HPC, 1SPC, 11 FVPCs, 7 FAs, 4 FCs, and 1HC. RET+ tumors included 4 HAs, 3 HCs, 1HPC, 12 PCs, 7 FVPCs, and 2 FAs. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a RET transcript in 6 Hurthle cell lesions. RET immunoreactivity is less sensitive and specific for PC than CK19. CK19 is useful for identifying PC, although only lesions with diffuse, intense staining should be considered positive. The detection of RET protein by immunohistochemical analysis was corroborated by the presence of the RET transcript by RT-PCR. Further study is warranted to determine whether this represents activation by gene fusion or some other mechanism in this subset of thyroid neoplasms.
UI - 12162679
AU - Renshaw AA
TI - Focal features of papillary carcinoma of the thyroid in fine-needle aspiration material are strongly associated with papillary carcinoma at resection.
SO - Am J Clin Pathol 2002 Aug;118(2):208-10
AD - Department of Pathology, Baptist Hospital of Miami, FL 33176, USA.
The cytologic features of papillary carcinoma of the thyroid in fine-needle aspiration material have been well described. The significance of finding these features in only a small population of cells is not well characterized. I reviewed the results of 28 thyroid fine-needle aspirates processed as direct smears and cell blocks in which only a small population (<20 cells) showed features of papillary carcinoma. Papillary carcinoma was considered in 142 (8.98%) of 1,581 aspirates, and in 28 cases (1.77%), 20 cells or fewer showed features of papillary carcinoma and follow-up was available. Papillary carcinomas greater than 1 cm were identified in 11 cases (39%; 3 follicular variants), papillary carcinomas less than 1 cm were identified in 4 cases (14%), and benign lesions in the remaining 13 cases (46%). The background material (either scant or abundant benign epithelium) did not correlate significantly with the result of resection. Identifying features of papillary carcinoma in a small population of cells in either a scant or an abundant thyroid aspirate are associated with a high rate of papillary carcinomas at resection, only a minority of which represent either the follicular variant or incidental tumors.
UI - 11841953
AU - Hanna CE; LaFranchi SH
TI - Adolescent thyroid disorders.
SO - Adolesc Med 2002 Feb;13(1):13-35, v
AD - Department of Pediatrics, Doernbecher Children's Hospital, Oregon Health Sciences University, Portland, 97201, USA.
Thyroid disorders are common in adolescence. Thyroid nodules can present in this age group, and although most are benign, malignancy is not unheard of. Chronic lymphocytic thyroiditis can present as hypothyroidism, while the adolescent with a goiter due to autoimmune thyroid disease is frequently euthyroid. Graves disease is a common etiology of hyperthyroid presentation in this age group. While there are known genetic and iatrogenic conditions that may predispose thyroid problems, they may also happen randomly in the general population. Thyroid problems may present as a goiter, a nodule, or a general cluster of abnormal symptoms and physical findings. The unique challenge to the provider of adolescent health care is that thyroid problems can adversely affect growth and development during puberty, a crucial period of hormonal interaction. This chapter addresses the diagnosis, treatment alternatives, and prognosis for a variety of common and uncommon thyroid abnormalities in adolescents. Many are readily treatable if recognized promptly, and even thyroid cancer often can be effectively treated and managed. Physicians treating the adolescent population have to be aware of the various thyroid problems that their patients can face.
UI - 12163389
AU - Poulaki V; Mitsiades CS; Kotoula V; Tseleni-Balafouta S; Ashkenazi A;
TI - Koutras DA; Mitsiades N Regulation of Apo2L/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in thyroid carcinoma cells.
SO - Am J Pathol 2002 Aug;161(2):643-54
AD - Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA. email@example.com
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)/Apo2 ligand selectively kills neoplastic cells, including thyroid carcinoma cells (Mitsiades et al: Thyroid carcinoma cells are resistant to FAS-mediated apoptosis but sensitive to tumor necrosis factor-related apoptosis-inducing ligand. Cancer Res 2000, 60:4122-41299). We investigated the mechanisms regulating Apo2L/TRAIL-induced apoptosis in thyroid carcinoma cells, as well as the impact of insulin-like growth factor (IGF)-1, interferon-gamma, and TNF-alpha. We found that the emergence of resistance to Apo2L/TRAIL, after prolonged incubation with this cytokine, was associated with increased levels of FLICE inhibitory protein (FLIP), and was overcome by cycloheximide and bisindolylmaleimide, that specifically down-regulated FLIP expression, as well as by transfection of a FLIP anti-sense oligonucleotide. IGF-1 activated Akt; up-regulated the caspase inhibitors FLIP, cIAP-2, XIAP, and survivin; and attenuated Apo2L/TRAIL-induced apoptosis. This effect was inhibited by the IGF-1 receptor neutralizing antibody aIR3, the PI-3K inhibitor wortmannin, and the heat shock protein-90 chaperone inhibitor geldanamycin. Transfection of constitutively active Akt protected from TRAIL. Conversely, interferon-gamma and TNF-alpha had a sensitizing effect. We conclude that FLIP may negatively regulate Apo2L/TRAIL-induced apoptosis in thyroid carcinomas. Microenvironmental paracrine survival factors, such as IGF-1, up-regulate caspase inhibitors, including FLIP, and protect from Apo2L/TRAIL in a PI-3K/Akt-dependent manner. T helper-1 cytokines and compounds that selectively abrogate the IGF-1 signaling pathway may be helpful adjunct agents in Apo2L/TRAIL-based anti-cancer therapeutic regimens.
UI - 12168961
AU - Rodriguez GJ; Balsalobre MD; Pomares F; Torregrosa NM; Rios A; Carbonell
TI - P; Glower G; Sola J; Tebar J; Parrilla P Prophylactic thyroidectomy in MEN 2A syndrome: experience in a single center.
SO - J Am Coll Surg 2002 Aug;195(2):159-66
AD - Department of Surgery, Virgen de la Arrixaca Hospital, Murcia, Spain.
BACKGROUND: Genetic study of the RET proto-oncogene has modified the management, treatment, and prognosis of medullary thyroid carcinoma (MTC), multiple endocrine neoplasia 2A (MEN 2A), for patients with less advanced tumor stages. Classically, the diagnosis was based on an increase in basal and poststimulus peak calcitonin (bCT and pCT). Prophylactic thyroidectomy, based on results of genetic testing, may reduce recurrences in MTC. STUDY DESIGN: Of 82 MTC (MEN 2A) patients genetically diagnosed and surgically treated at our center, 22 received a prophylactic thyroidectomy (RET +, bCT and pCT with normal values and asymptomatic). We analyzed age, gender, phenotype, RET mutation, cervical ultrasound, laboratory tests (bCT, pCT, and CEA), surgery, histologic data, TNM, and followup. RESULTS: The 22 patients belonged to 8 families with MTC (MEN 2A). Mean age was 15.2 years (range 5 to 36 years). The RET mutation in 21 patients was Cys-->Tyr and in the remaining patient both in codon 634 in exon 11. The median values of bCT and pCT were 38 pg/mL (range < 15 to 75 pg/mL) and 148.5 pg/mL (range < 15 to 250 pg/mL), respectively. Total thyroidectomy was performed in 8 patients (age < or = 10 years) and associated central neck dissection in 14 patients (age> 10 years). Histologic study showed 7 C-cell hyperplasias and 15 MTCs (8 bilateral); the median size was 0.2 cm (range < 0.1 to 0.7cm); 1 patient had metastatic adenopathies. According to TNM, 7 were stage 0, 14 were stage I, and 1 was stage III. Postsurgery bCT and pCT values were normal in all patients, with a curative rate of 100%. MTC patients compared with C-cell hyperplasia patients were older on average, had higher mean bCT, mean pCT, and mean CEA. CONCLUSIONS: Prophylactic thyroidectomy based on genetic testing allows identification and treatment of patients at an early stage of the disease and decreases recurrence rates. pCT values above the upper limit of normal may be markers for the presence of MTC and should be considered in selecting operative procedures for these patients.
UI - 12175525
AU - Hasegawa Y; Takano T; Miyauchi A; Matsuzuka F; Yoshida H; Kuma K; Amino
TI - N Decreased expression of glutathione peroxidase mRNA in thyroid anaplastic carcinoma.
SO - Cancer Lett 2002 Aug 8;182(1):69-74
AD - Department of Laboratory Medicine, Osaka University Medical School, D2, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Our recent study using serial analysis of gene expression show the decreased expression of glutathione peroxidase (GPx), an antioxidant enzyme, in an anaplastic carcinoma. To clarify the expression of GPx in various kinds of thyroid tumors, the expression levels of GPx mRNA in 79 benign and malignant thyroid tissues were measured by means of real-time quantitative reverse transcription-polymerase chain reaction. A decreased expression of GPx mRNA was observed in all of five anaplastic carcinomas and some of the papillary carcinomas. A molecular-based therapy which produces O(2) radical may be considered as an alternative choice for the treatment of anaplastic carcinomas.
UI - 12053214
AU - Vestergaard H; OStergaard Kristensen L
TI - Normocalcemia and persistent elevated serum concentrations of 1-84 parathyroid hormone after operation for sporadic parathyroid adenoma: evidence of increased morbidity from cardiovascular disease.
SO - World J Surg 2002 Jun;26(6):657-60
AD - Department of Endocrinology, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark. firstname.lastname@example.org
Elevated serum concentrations of 1-84 parathyroid hormone (PTH) after operation for sporadic parathyroid adenoma have been reported in previous studies, years after operation for primary hyperparathyroidism (pHPT). The cause and significance of this finding have not been elucidated. Primary hyperparathyroidism was diagnosed in 195 patients 124 patients. To evaluate long-term effects of elevated serum 1-84 PTH, biochemical variables and pre- and postoperative diseases were investigated from hospital case records. Of the 124 patients operated on, 103 had a solitary adenoma. Among these patients, 60 had normal serum concentrations of 1-84 PTH and calcium postoperatively, 38 patients had follow-up for more than 12 months (range 12-207 months-group A). Persistent elevated serum concentrations of 1-84 PTH and normocalcemia were found in 23 patients. Fourteen patients had follow-up for more than 12 months (range 15-76 months-group B). Two patients had persistent pHPT, and 18 were normocalcemic, but in this retrospective study data on serum 1-84 PTH were not available. No significant differences were found between groups A and B at the time of diagnosis concerning clinical characteristics. More that 12 months after operation for pHPT, the patients in group B, with persistent elevated serum concentrations of 1-84 PTH, had a significantly (c2 = 11, p = 0.005, and power of test 0.66) higher frequency of cardiovascular diseases from ischemic heart disease and hypertension. Persistent elevated serum concentrations of 1-84 PTH after operation for sporadic parathyroid adenoma may be associated with development of cardiovascular disease. This group of patients therefore needs lifelong control and, possibly, medical intervention.
UI - 12170087
AU - Decaussin M; Bernard MH; Adeleine P; Treilleux I; Peix JL; Pugeat M;
TI - Tourniaire J; Berger N Thyroid carcinomas with distant metastases: a review of 111 cases with emphasis on the prognostic significance of an insular component.
SO - Am J Surg Pathol 2002 Aug;26(8):1007-15
AD - Department of Pathology, Hopital de l'Antiquaille, Lyon, France.
Distant metastases (DM) are rare in well-differentiated thyroid carcinomas and correlate with a poor survival. Among the histologic subtypes, insular carcinoma has an intermediate prognosis that lies between well and undifferentiated carcinomas. To assess the characteristics that could predict a worse prognosis, we reviewed the initial thyroid cancer slides from patients with DM. We achieved a comparative statistical analysis with a control group without DM. Among 1230 differentiated carcinomas treated from 1960 to 1999, 9% developed DM. In this group the mean age was 53 years, with a 73% rate of death. The histologic slides were available in 80 cases. The primary thyroid tumors were classified as papillary (51 cases), follicular (25), and pure insular carcinomas (4). Extrathyroidal extension was present in 47% of papillary carcinomas. The mean tumor size was above 5 cm for all the histologic subtypes, and at least a vascular invasion was found in 69%. Fifty-four percent of these tumors had an insular component compared with only 6.5% in the control group. The statistical analysis confirmed by univariate and multivariate logistic regression that the risk of DM was highly elevated in the presence of insular carcinoma. Our study indicates that elevated age, large tumor size, vascular invasion, and extrathyroidal extension are important prognostic factors in well-differentiated carcinomas. We also demonstrate that the presence of an insular component in an otherwise differentiated carcinoma is a strong independent poor prognostic factor.
UI - 12170088
AU - Nikiforova MN; Biddinger PW; Caudill CM; Kroll TG; Nikiforov YE
TI - PAX8-PPARgamma rearrangement in thyroid tumors: RT-PCR and immunohistochemical analyses.
SO - Am J Surg Pathol 2002 Aug;26(8):1016-23
AD - Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0529, USA. Yuri.Nikiforov@uc.edu
A PAX8-PPARgamma rearrangement has been recently identified in follicular thyroid carcinomas, but not in follicular adenomas or other thyroid tumors. We report here the analyses of PAX8-PPARgamma in a series of 118 thyroid tumors using a newly developed RT-PCR assay to detect this rearrangement in frozen and paraffin-embedded tissues and using immunostaining with a PPARgamma antibody. PAX8-PPARgamma was detected by RT-PCR in eight of 15 (53%) follicular carcinomas and two of 25 (8%) follicular adenomas but not in 35 papillary carcinomas (including 12 follicular variants), 12 Hurthle cell carcinomas, 12 Hurthle cell adenomas, two anaplastic carcinomas, one poorly differentiated carcinoma, or 16 hyperplastic nodules. The prevalence was higher in follicular carcinomas from patients with a history of radiation exposure (three of three). Strong, diffuse nuclear immunostaining with the PPARgamma antibody correlated with the presence of PAX8-PPARgamma detected by RT-PCR. Most sporadic follicular carcinomas positive for PAX8-PPARgamma were overtly invasive, whereas tumors lacking the rearrangement were predominantly minimally invasive. The two follicular adenomas positive for PAX8-PPARgamma had trabecular growth pattern and thick capsule, but no invasion, and thus may represent "pre-invasive" follicular carcinomas. The absence of PAX8-PPARgamma rearrangements in Hurthle cell tumors and papillary thyroid carcinomas highlights the differences in the molecular pathogenesis of these thyroid tumors.
UI - 12161532
AU - Shattuck TM; Costa J; Bernstein M; Jensen RT; Chung DC; Arnold A
TI - Mutational analysis of Smad3, a candidate tumor suppressor implicated in TGF-beta and menin pathways, in parathyroid adenomas and enteropancreatic endocrine tumors.
SO - J Clin Endocrinol Metab 2002 Aug;87(8):3911-4
AD - Center for Molecular Medicine and Division of Endocrinology and Metabolism, University of Co