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1.
Clin Endocrinol (Oxf) ; 74(1): 21-9, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21039729

ABSTRACT

AIMS AND METHODS: The aim of this prospective study was to compare the diagnostic value of [¹8F]FDOPA-PET and [¹¹¹In]pentetreotide-SPECT somatostatin receptor scintigraphy (SRS) in patients with nonmetastatic extra-adrenal paragangliomas (PGLs). Twenty-five consecutive unrelated patients who were known or suspected of having nonmetastatic extra-adrenal PGLs were prospectively evaluated with SRS and [¹8F]FDOPA-PET. ¹³¹I-MIBG and [¹8F]FDG-PET were added to the work-up in patients with a personal or familial history of PGL, predisposing mutations, abdominal PGLs, metanephrine hypersecretion and abdominal foci on SRS and/or [¹8F]FDOPA-PET. RESULTS: SRS correctly detected 23/45 lesions of which 20 were head or neck lesions (H&N) and 3 were abdominal lesions. [¹8F]FDOPA-PET detected significantly more lesions than SRS (39/45, P < 0·001). Both SRS and ¹8F-DOPA-PET detected significantly more H&N than abdominal lesions (66·7% vs 20%, P = 0·003 and 96·7% vs 67%, P = 0·012, respectively). In two patients with the succinate dehydrogenase D (SDHD) mutation, [¹8F]FDOPA-PET missed five abdominal PGLs which were detected by the combination of SRS, [¹³¹I]MIBG and [¹8F]FDG-PET. A lesion-based analysis using a forward stepwise logistic regression model demonstrates that size ≤ 10 mm (P = 0·002) and abdominal lesions (P = 0·031) were independently associated with "[¹8F]FDOPA-PET diagnosis only". In turn, a previous history of surgery and/or the presence of germline mutation was associated with lower lesion size (P = 0·001). CONCLUSIONS: The sensitivity of SRS for localizing parasympathetic PGLs is lower than originally reported, and [¹8F]FDOPA-PET is better than SRS for localizing small lesions. SRS should be replaced by [¹8F]FDOPA-PET as the first-line imaging procedure in H&N PGL, especially in patients at risk of multifocal disease (predisposing mutations and or previous history of surgery).


Subject(s)
Paraganglioma, Extra-Adrenal/diagnosis , Positron-Emission Tomography , Somatostatin/analogs & derivatives , Tomography, Emission-Computed, Single-Photon/methods , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Paraganglioma, Extra-Adrenal/metabolism , Prospective Studies , Receptors, Somatostatin/metabolism , Young Adult
2.
J Clin Endocrinol Metab ; 95(7): 3283-90, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20392868

ABSTRACT

CONTEXT: A few prospective studies have evaluated the use of recombinant human TSH (rhTSH) for radioiodine remnant ablation. OBJECTIVE: Our objective was to compare the effects of the both TSH regimens on iodine biokinetics in the thyroid remnant, dosimetry, and radiation protection. DESIGN: We conducted a prospective randomized study. MATERIALS AND METHODS: Eighty-eight patients were enrolled for radioiodine ablation to either the hypothyroid or rhTSH arms. A whole-body scan was performed at 48 and 144 h after therapy. Dose rates were assessed at 24, 48, and 144 h. Urinary samples were obtained during the first 48 h. Thyroglobulin was assessed before and after therapy. Iodine biokinetics in the remnants were calculated from gamma-count rates. Radiation-absorbed dose was calculated using OLINDA software. Exposure estimation was based on a validated model. RESULTS: The effective half-life in the remnant thyroid tissue was significantly longer after rhTSH than during hypothyroidism (P = 0.01), whereas 48-h (131)I uptakes and residence times were similar. After therapy, thyroglobulin release (a marker of cell damage) was lower in the rhTSH arm. The mean total-body effective half-life and residence time were shorter in patients treated after rhTSH. Residence time was also lower for the colon and stomach. Absorbed dose estimates were lower in the rhTSH arm for the lower large intestine, breasts, ovaries, and the bone marrow. Dose rates at the time of discharge were lower in the rhTSH group with a reduction in cumulative radiation exposure to contact persons. CONCLUSIONS: In comparison with thyroid hormone withdrawal, rhTSH is associated with longer remnant half-life of radioactive iodine while also reducing radiation exposure to the rest of the body and also to the general public who come in contact with such patients.


Subject(s)
Ablation Techniques/methods , Adenocarcinoma, Follicular/radiotherapy , Carcinoma, Papillary/radiotherapy , Iodine Radioisotopes/therapeutic use , Iodine/metabolism , Thyroid Neoplasms/radiotherapy , Thyrotropin/therapeutic use , Adenocarcinoma, Follicular/surgery , Carcinoma, Papillary/surgery , Combined Modality Therapy , Half-Life , Humans , Prospective Studies , Radiometry , Recombinant Proteins/therapeutic use , Thyroid Gland/radiation effects , Thyroid Neoplasms/surgery , Thyroxine/therapeutic use , Treatment Outcome , Triiodothyronine/therapeutic use
3.
Br J Surg ; 97(5): 684-90, 2010 May.
Article in English | MEDLINE | ID: mdl-20235084

ABSTRACT

BACKGROUND: Not operating on patients with mild hypercalcitoninaemia (MHCT) and sporadic thyroid disease carries the risk of omitting curative surgery for medullary thyroid cancer, but systematic surgery would result in unnecessary treatment of benign pathology. This study reviewed the management of MCHT and non-hereditary thyroid disease in one centre. METHODS: MCHT was defined as an increase in basal and stimulated calcitonin levels not exceeding 30 and 200 pg/ml respectively. Over 15 years, 125 patients who presented with MCHT and sporadic thyroid disease were followed. Surgery was indicated only if there were local pressure symptoms or suspicious histomorphological changes in solitary nodules. RESULTS: Fifty-five patients underwent total thyroidectomy and 18 unilateral total lobectomy. Histological examination revealed medullary microcarcinoma in six patients (two women and four men). C-cell hyperplasia was found in 54 patients (74 per cent) and 13 (18 per cent) harboured no C-cell pathology. Calcitonin levels stabilized after lobectomy and became undetectable following thyroidectomy. They normalized during follow-up in a third of patients who did not have surgery. CONCLUSION: Not all patients with MHCT and sporadic thyroid disease require surgery.


Subject(s)
Biomarkers, Tumor/blood , Calcitonin/blood , Thyroid Diseases/diagnosis , Thyroid Gland/pathology , Thyroidectomy , Carcinoma, Medullary/diagnosis , Diagnosis, Differential , Female , Humans , Hyperplasia/diagnosis , Male , Middle Aged , Thyroid Diseases/surgery , Thyroid Gland/surgery , Thyroid Neoplasms/diagnosis , Unnecessary Procedures
4.
World J Surg ; 34(4): 830-5, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20145930

ABSTRACT

BACKGROUND: Medullary thyroid cancer (MTC) is characterized by early regional lymph node metastasis, the presence of which represents a critical obstacle to cure. At present no molecular markers have been successfully integrated into the clinical care of sporadic MTC. The present study was designed to evaluate TP53INP1 expression in MTC and to assess its ability to guide the surgeon to the optimal extent of surgery performed with curative intent. METHODS: Thirty-eight patients with sporadic MTC were evaluated. TP53INP1 immunoexpression was studied on embedded paraffin material and on cytological smears. RESULTS: TP53INP1 was expressed in normal C cells, in C-cell hyperplasia, and in 57.9% of MTC. It was possible to identify two groups of MTC according to the proportion of TP53INP1 expressing tumor cells: group 1 from 0% to <50% and group 2 from 50% to 100% of positive cells. Patients with a decreased expression of TP53INP1 (group 1) had a lower rate of nodal metastasis (18.8% versus 63.4% in group 2; P = 0.009), with only minimal lymph node involvement per N1 patient (2.7% of positive lymph nodes versus 22.9%; P < 0.001) and better outcomes (100% of biochemical cure versus 55.5%; P < 0.001). Patients with distant metastases were only observed in group 2. Cytological samples exhibit similar results to their embedded counterparts. CONCLUSIONS: TP53INP1 immunoexpression appears to be a clinical predictor of lymph node metastasis in MTC. The evaluation of TP53INP1 expression may guide the extent of lymph node dissection in the clinically node-negative neck. These findings require prospective validation.


Subject(s)
Carcinoma, Medullary/metabolism , Carrier Proteins/metabolism , Heat-Shock Proteins/metabolism , Thyroid Neoplasms/metabolism , Adult , Aged , Biomarkers, Tumor/metabolism , Blotting, Western , Carcinoma, Medullary/pathology , Carcinoma, Medullary/surgery , Chi-Square Distribution , Female , Humans , Immunohistochemistry , Logistic Models , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Statistics, Nonparametric , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery
5.
J Clin Endocrinol Metab ; 95(1): 303-7, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19915018

ABSTRACT

CONTEXT: Fluorine-18-L-dihydroxyphenylalanine positron emission tomography (18F-FDOPA PET) imaging is increasingly used in the workup of neuroendocrine tumors. It has been shown to be an accurate tool in the diagnosis of congenital hyperinsulinism, but limited information is available on its value in adult disease. OBJECTIVE, PATIENTS, AND DESIGN: The objective of this study was to review our experience with 18F-FDOPA PET imaging in six consecutive patients with hyperinsulinemic hypoglycemia (HH) (four solitary insulinomas, one diffuse beta-cell hyperplasia, one malignant insulinoma). 18F-FDOPA uptake was also evaluated in 37 patients (43 procedures) without HH or other pancreatic neuroendocrine tumors, which acted as a control group. RESULTS: Using visual analysis, 18F-FDOPA-PET proved positive in only one case (a multiple endocrine neoplasia type 1 related insulinoma). In diffuse beta-cell hyperplasia, the pancreatic uptake was similar to controls. In the patient with liver metastases, the extent of disease was underestimated. The pancreatic uptake was not statistically different between controls and hyperinsulinemic patients. The main limitation for identifying insulinomas or beta-cell hyperplasia in adults appears to be to the 18F-FDOPA uptake and retention in the whole pancreas. This drawback is potentially circumvented in focal hyperplasia in newborns due to a lower aromatic amino acid decarboxylase expression in the extralesional pancreatic parenchyma. CONCLUSIONS: 18F-FDOPA PET is of limited value in localizing pancreatic insulin secreting tumors in adult HH. Our results contrast with the referential study and require further analysis.


Subject(s)
Dihydroxyphenylalanine , Hyperinsulinism/complications , Hypoglycemia/complications , Insulinoma/diagnostic imaging , Pancreatic Neoplasms/diagnostic imaging , Positron-Emission Tomography/methods , Adolescent , Adult , Aged , Child , Dihydroxyphenylalanine/analogs & derivatives , Female , Humans , Hyperinsulinism/diagnostic imaging , Hypoglycemia/diagnostic imaging , Insulin-Secreting Cells/diagnostic imaging , Insulin-Secreting Cells/pathology , Insulinoma/complications , Male , Middle Aged , Pancreatic Neoplasms/complications , Predictive Value of Tests , Retrospective Studies , Young Adult
6.
Clin Endocrinol (Oxf) ; 71(1): 115-23, 2009 Jul.
Article in English | MEDLINE | ID: mdl-18803678

ABSTRACT

BACKGROUND: Recombinant human TSH (rhTSH) has become the modality of choice for radioiodine remnant ablation (RRA) in low-risk thyroid cancer patients. AIMS AND METHODS: The aims of the present prospective randomized study were to evaluate the impact of TSH stimulation procedure (hypothyroidism vs. rhTSH) on quality of life (QoL) of thyroid cancer patients undergoing RRA and to evaluate efficacy of both procedures. L-T4 was initiated in both groups after thyroidectomy. After randomization, L-T4 was discontinued in hypothyroid (hypo) group and continued in rhTSH group. A measure of 3.7 GBq of radioiodine was given to both groups. The functional assessment of chronic illness therapy-fatigue (FACIT-F) was administered from the early postoperative period to 9 months. Socio-demographic parameters, anxiety and depression scales were also evaluated (CES-D, BDI and Spielberger state-trait questionnaires). At 9 months, patients underwent an rhTSH stimulation test, diagnostic (131)I whole body scan (dxWBS) and neck ultrasonography. RESULTS: A total of 74 patients were enrolled for the study. There was a significant decrease in QoL from baseline (t0) to t1 (RRA period) in the hypothyroid group with significant differences in FACIT-F TOI (P < 10(-3)), FACT-G total score (P = 0.005) and FACIT-F total score (P = 0.003). By contrast, QoL was preserved in the rhTSH group. In the multivariate analysis, FACIT-TOI changes were only affected by the modality of TSH stimulation performed for RRA. From 3 to 9 months, changes of QoL scales and subscales were no longer statistically different in both groups of patients. Based on serum rhTSH-stimulated Tg alone (Tg < 0.8 microg/l, BRAHMS Tg Kryptor), no difference in ablation success was observed between rhTSH and hypothyroidism groups, 91.7% and 97.1%, respectively. A higher rate of persistent thyroid remnants was observed in the rhTSH arm, although in most cases uptake was < 0.1% and of no clinical significance. CONCLUSIONS: rhTSH preserves QoL of patients undergoing RRA with similar rates of ablation success compared to hypothyrodism. However, there is a wide heterogeneity in the clinical impact of hypothyroidism.


Subject(s)
Iodine Radioisotopes/therapeutic use , Quality of Life , Thyroid Neoplasms/drug therapy , Thyrotropin/therapeutic use , Adult , Female , Humans , Male , Middle Aged , Prospective Studies , Recombinant Proteins/therapeutic use , Treatment Outcome
7.
Diabetes Metab ; 34(4 Pt 1): 343-8, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18556231

ABSTRACT

AIM: Sporadic malignant insulinoma (SMI) is a rare disease, and the consequent paucity of data in the literature and the development of aggressive treatments for liver metastases have led us to retrospectively analyze a series of 12 cases of SMI. METHODS: Every patient presenting with SMI, according to the WHO 2004 histopathology criteria, between 1970 and June 2005 in Marseille was included in the study. Patients with multiple endocrine neoplasia type 1 (MEN-1) and tumours of uncertain malignant potential were excluded. RESULTS: The ratio of male/female was 4/8, and mean age at diagnosis was 52.5 years. A 48-h fasting test in 10 patients was conclusive in nine, after a mean duration of 12 h 45 min. SMI size ranged from 7-120 mm (mean 30.3mm). Six patients had liver metastases and one had isolated lymph-node invasion. Surgery was performed in 12 patients. Five persisting diseases (mean follow-up of 1.8 years) required other treatments (chemoembolization, radiofrequency thermoablation [RFTA], liver transplantation); one patient relapsed 8.5 years after surgery; six were still in complete remission (mean follow-up of 5.8 years), and one patient had died by the time of the 24-month follow-up. CONCLUSION: Aggressive sequential multimodal therapy can prolong the survival of patients with SMI even in the presence of liver metastases.


Subject(s)
Insulinoma/therapy , Pancreatic Neoplasms/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy/mortality , Female , Follow-Up Studies , Humans , Insulinoma/mortality , Insulinoma/secondary , Insulinoma/surgery , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Male , Middle Aged , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/surgery , Prognosis , Retrospective Studies , Survival Rate
8.
Eur J Nucl Med Mol Imaging ; 35(11): 2018-25, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18566816

ABSTRACT

PURPOSE: The widespread use of high-resolution cross-sectional imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) for the investigation of the abdomen is associated with an increasing detection of incidental adrenal masses. We evaluated the ability of (18)F-fluorodeoxyglucose positron emission tomography to distinguish benign from malignant adrenal masses when CT or MRI results had been inconclusive. METHODS: We included only patients with no evidence of hormonal hypersecretion and no personal history of cancer or in whom previously diagnosed cancer was in prolonged remission. PET/CT scans were acquired after 90 min (mean, range 60-140 min) after FDG injection. The visual interpretation, maximum standardised uptake values (SUVmax) and adrenal compared to liver uptake ratio were correlated with the final histological diagnosis or clinico-radiological follow-up when surgery had not been performed. RESULTS: Thirty-seven patients with 41 adrenal masses were prospectively evaluated. The final diagnosis was 12 malignant, 17 benign tumours, and 12 tumours classified as benign on follow-up. The visual interpretation was more accurate than SUVmax alone, tumour diameter or unenhanced density, with a sensitivity of 100% (12/12), a specificity of 86% (25/29) and a negative predictive value of 100% (25/25). The use of 1.8 as the threshold for tumour/liver SUVmax ratio, retrospectively established, demonstrated 100% sensitivity and specificity. CONCLUSION: FDG PET/CT accurately characterises adrenal tumours, with an excellent sensitivity and negative predictive values. Thus, a negative PET may predict a benign tumour that would potentially prevent the need for surgery of adrenal tumours with inconclusive conventional imaging.


Subject(s)
Adrenal Gland Neoplasms/diagnosis , Fluorodeoxyglucose F18 , Incidental Findings , Adrenal Gland Neoplasms/diagnostic imaging , Adrenal Gland Neoplasms/pathology , Female , Humans , Male , Middle Aged , Positron-Emission Tomography , Reproducibility of Results , Sensitivity and Specificity , Tomography, X-Ray Computed
9.
Clin Endocrinol (Oxf) ; 69(4): 580-6, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18394015

ABSTRACT

BACKGROUND: (18)F-DOPA has emerged as a promising tool in the localization of chromaffin-tissue-derived tumours. Interestingly, phaeochromocytomas (PHEO) are also FDG avid. AIM AND METHODS: The aim of this study was to retrospectively evaluate the results of (18)F-FDOPA and/or (18)F-FDG-PET in patients with PHEO and paragangliomas (PGLs) and to compare the outcome of this approach with the traditional therapeutic work-up. Nine patients with non-MEN2 related PHEO or PGL were evaluated. At the time of the PET studies, the patients were classified into three groups based on their clinical history, conventional and SPECT imaging. The groups were malignant disease (n = 5, 1 VHL), apparently unique tumour site in patients with previous surgery (n = 1, SDHB) and multifocal tumours (n = 3, 1 VHL, 1 SDHD). (18)F-FDOPA and (18)F-FDG-PET PET/CT were then performed in all patients. RESULTS: PET successfully identified additional tumour sites in five out of five patients with metastatic disease that had not been identified with SPECT + CI. Whilst tumour tracer uptake varied between patients it exhibited a consistently favourable residence time for delayed acquisitions. (18)F-FDOPA uptake (SUVmax) was superior to (18)F-FDG uptake in cases of neck PGL (three patients, four tumours). If only metastatic forms and abdominal PGLs were considered, (18)F-FDG provided additional information in three cases (two metastatic forms, one multifocal disease with SDHD mutation) compared to (18)F-FDOPA. CONCLUSIONS: Our results suggest that tumour staging can be improved by combining (18)F-FDOPA and (18)F-FDG in the preoperative work-up of patients with abdominal and malignant PHEOs. (18)F-FDOPA is also an effective localization tool for neck PGLs. MIBG however, still has a role in these patients as MIBG and FDOPA images did not completely overlap.


Subject(s)
Adrenal Gland Neoplasms/diagnostic imaging , Dihydroxyphenylalanine/analogs & derivatives , Fluorodeoxyglucose F18 , Pheochromocytoma/diagnostic imaging , Positron-Emission Tomography/methods , 3-Iodobenzylguanidine , Adrenal Gland Neoplasms/pathology , Adult , Aged , Dihydroxyphenylalanine/adverse effects , Dihydroxyphenylalanine/chemistry , Dihydroxyphenylalanine/pharmacokinetics , Disease Progression , Female , Fluorodeoxyglucose F18/adverse effects , Fluorodeoxyglucose F18/pharmacokinetics , Humans , Male , Middle Aged , Neoplasms, Multiple Primary/diagnostic imaging , Neoplasms, Multiple Primary/pathology , Pheochromocytoma/pathology , Retrospective Studies , Tomography, Emission-Computed, Single-Photon/methods
10.
Histopathology ; 52(5): 623-30, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18370959

ABSTRACT

AIMS: To evaluate the reliability of desmoplasia as a reproducible morphological parameter indicating the metastatic potential of medullary thyroid carcinoma (MTC). METHODS AND RESULTS: One hundred and twenty cases of MTC of the Medical University of Vienna, Austria and 76 cases from the School of Medicine of Marseille, France were analysed for the presence of desmoplastic stroma reaction by four endocrine pathologists. Intra- and interobserver concordance was assessed. The Austrian cases were also analysed for various morphological parameters. Intra- and interobserver concordance were highly significant with a kappa value of 0.883 for intra-observer reliability and 0.837, 0.79 and 0.758, respectively, when pathologists N.N., C.D.M. and K.W.S. reviewed the Austrian cases. The cases from France were reviewed by C.D.M. and K.K. with a kappa value of 0.759. None of the cases that were categorized as desmoplasia negative by any of the investigators showed lymph node metastasis. No other distinct morphological characteristics could be assigned to the MTCs without desmoplasia. CONCLUSIONS: Our data indicate desmoplasia to be a reliable and highly reproducible parameter with regard to lymph node metastatic potential.


Subject(s)
Carcinoma, Medullary/diagnosis , Thyroid Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Carcinoma, Medullary/metabolism , Carcinoma, Medullary/secondary , Collagen , Female , Fibrosis , Humans , Immunohistochemistry , Lymph Nodes/pathology , Lymphatic Metastasis/diagnosis , Male , Middle Aged , Observer Variation , Predictive Value of Tests , Reproducibility of Results , Stromal Cells/metabolism , Stromal Cells/pathology , Thyroid Neoplasms/metabolism
11.
Br J Cancer ; 98(4): 818-23, 2008 Feb 26.
Article in English | MEDLINE | ID: mdl-18212751

ABSTRACT

The purpose of this study was to compare the diagnostic interest of Hector Battifora mesothelial antigen-1 (HBME-1), thyroid peroxidase (TPO), and dipeptidyl aminopeptidase IV (DPP4) in thyroid fine-needle aspirates obtained from 200 resected thyroid lesions (55 colloid nodules, 54 follicular adenomas, 59 papillary cancers, and 32 follicular carcinomas). Hector Battifora mesothelial antigen-1 or TPO expression (% positive cells) and DPP4 staining score (12-point scale) were evaluated. Receiver operating characteristic (ROC) curves were plotted and optimal cutoff values for diagnosing malignancy were determined. The TPO ROC curve was consistently higher than the HBME-1 ROC curve. The TPO curve was also higher than the DPP4 curve with regard to sensitivity, but dipped below the DPP4 curve with regard to specificity. Using a cutoff value of <80% positive cells for TPO, >10% positive cells for HBME-1, and staining score > or =1 for DPP4, sensitivity to specificity ratios were 98-83% for TPO, 90-60% for HBME-1, and 88-80% for DPP4. Two particularly interesting findings of this study were the low negative likelihood ratio of TPO (0.02) allowing highly reliable exclusion of malignancy and the 100% specificity of DPP4 staining scores=12. Due to poor performance on follicular lesions, HBME-1 showed no advantage over TPO or DPP4.


Subject(s)
Adenocarcinoma, Follicular/metabolism , Autoantigens/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Papillary/metabolism , Dipeptidyl Peptidase 4/metabolism , Iodide Peroxidase/metabolism , Iron-Binding Proteins/metabolism , Thyroid Neoplasms/metabolism , Adenocarcinoma, Follicular/diagnosis , Biomarkers, Tumor/analysis , Biopsy, Fine-Needle , Biopsy, Needle , Carcinoma, Papillary/diagnosis , Cytodiagnosis , Humans , Immunoenzyme Techniques , ROC Curve , Sensitivity and Specificity , Thyroid Neoplasms/diagnosis , Thyroid Nodule/metabolism , Thyroid Nodule/pathology
12.
Br J Surg ; 94(5): 566-70, 2007 May.
Article in English | MEDLINE | ID: mdl-17380564

ABSTRACT

BACKGROUND: Distinction of parathyroid cancer from atypical parathyroid adenoma (APA) at operation is difficult. The aim of this study was to determine whether parathyroid cancer and APA have different operative findings and long-term outcomes. METHODS: A retrospective review was undertaken of patients with suspicious or malignant parathyroid tumours treated between 1974 and 2005. Parathyroid cancer was defined as a lesion with vascular or tissue invasion, and APA as a neoplasm with broad fibrous bands, trabecular growth, mitosis and nuclear atypia. RESULTS: Twenty-seven patients with suspicious or malignant parathyroid tumours were identified. After histological review, parathyroid cancer was confirmed in 11 patients (group 1) and 16 tumours were classified as APA (group 2). The clinical presentation and operative findings of the two types of tumour were indistinguishable. At initial surgery, seven patients in group 1 underwent en bloc resection, and four had parathyroidectomy. Four of the seven patients who had en bloc resection had recurrences. No recurrences were observed in the other seven patients in group 1 at a median follow-up of 65 months. In group 2, eight patients had en bloc resection and eight had parathyroidectomy; no patient had recurrence at a median follow-up of 91 months. CONCLUSION: Operative findings cannot distinguish APA from parathyroid cancer reliably. Without evidence of macroscopic local invasion, the value of en bloc resection at initial surgery remains debatable.


Subject(s)
Adenoma/diagnosis , Parathyroid Neoplasms/diagnosis , Parathyroidectomy/methods , Adenoma/surgery , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Intraoperative Period , Male , Middle Aged , Neoplasm Recurrence, Local/etiology , Parathyroid Neoplasms/surgery , Prognosis , Retrospective Studies , Treatment Outcome
13.
Endocr Relat Cancer ; 13(2): 485-95, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16728576

ABSTRACT

Immunocytochemistry (ICC) of thyroid peroxidase (TPO) using the monoclonal antibody MoAb47 has been used as malignancy marker on thyroid fine needle aspiration. However, little is known about the fate of TPO in thyroid carcinoma. We performed a qualitative PCR (Q-PCR) analysis to measure the expression of variants of tpo mRNA in 13 normal tissue samples, 30 benign tumors (BT), 21 follicular carcinomas (FC), 20 classical papillary carcinomas (PCc), 12 follicular variants of papillary carcinomas (PCfv) and nine oncocytic carcinomas (OC). We also studied mutations involving the ras, Braf, ret or pax8 genes. Results of Q-PCR were closely correlated with those of ICC (P < 0.0001; R = 0.59) and showed that overall tpo expression was lower in all carcinomas than in normal and BT (P < 0.05). The ratio tpo2 or tpo3 to tpo1 was inversed in follicular tumors. Genetic mutations were observed in 90% of PCc, 61.9% of FC, 41.7% of PCfv, 0% of OC and 10% in BT. pax8-ppar gamma1 rearrangement was correlated with qualitative changes in tpo mRNA (P < 0.01). These results confirmed the decrease of TPO expression in 97% of thyroid carcinomas regardless of histological type and the overexpression of shorter splice variants in follicular tumors. Both reduction in quantity of TPO and impairment of its maturation process could account for the atypical immunohistochemical reaction of MoAb47 with TPO.


Subject(s)
Carcinoma/enzymology , Gene Expression Regulation, Neoplastic , Genes, Neoplasm/genetics , Iodide Peroxidase/genetics , Thyroid Neoplasms/enzymology , Adult , Aged , Carcinoma/genetics , Down-Regulation , Female , Genes, ras/genetics , Humans , Iodide Peroxidase/analysis , Male , Middle Aged , Mutation , PAX8 Transcription Factor , Paired Box Transcription Factors/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins c-ret/genetics , RNA, Messenger/analysis , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Thyroid Neoplasms/genetics
14.
Ann Chir ; 131(3): 219-21, 2006 Mar.
Article in French | MEDLINE | ID: mdl-16242662

ABSTRACT

The diagnosis of thyroid nodules is straightforward and rarely mistaken. We present a case of a paraesophageal granular cell tumor, discovered incidentally during surgery for what it was diagnosed as a suspicious thyroid nodule by ultrasound and FNA. Complete resection was achieved without disruption of the esophageal mucosa. A terminal branch of the recurrent laryngeal nerve had to be resected en bloc with the tumor. Morphological and immunohistochemical diagnosis was established postoperatively. A review of the literature is presented.


Subject(s)
Adenocarcinoma/diagnosis , Esophageal Neoplasms/diagnosis , Thyroid Nodule/diagnosis , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Diagnosis, Differential , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Female , Humans , Middle Aged , Thyroid Nodule/pathology , Thyroid Nodule/surgery
15.
Endocr Relat Cancer ; 12(1): 173-83, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15788648

ABSTRACT

Like children exposed to Chernobyl fallout, the workers who cleaned up after the accident, also known as liquidators, have exhibited an increased incidence of thyroid cancer. A high prevalence of ret/PTC3 rearrangement has been found in pediatric post-Chernobyl thyroid tumors, but this feature has not been investigated in liquidator thyroid tumors. In this study we analyzed the prevalence of ret/PTC1 and ret/PTC3 in thyroid tumors from 21 liquidators, 31 nonirradiated adult Ukrainian patients, and 34 nonirradiated adult French patients. ret rearrangements in carcinomas were found in 83.3% of liquidators, 64.7% of Ukrainian patients, and 42.9% of French patients. The prevalence of ret/PTC1 was statistically similar in the three groups. The prevalence of ret/PTC3 was significantly higher in liquidators than in French patients (P = 0.03) but it was also high in nonirradiated Ukrainian patients who exhibited values intermediate between liquidators and French patients. In adenomas the prevalence of rearrangement was significantly higher in all Ukrainians than in French patients (P = 0.004). Like children exposed to Chernobyl fallout, liquidators showed a high prevalence of ret/PTC3. This finding suggests that irradiation had the same effect regardless of age. However, given the high rate of ret/PTC3 in nonirradiated adult Ukrainians, the possibility of genetic susceptibility or low-level exposure to radiation in that group cannot be excluded.


Subject(s)
Carcinoma, Papillary/etiology , Neoplasms, Radiation-Induced/etiology , Oncogene Proteins/genetics , Radioactive Hazard Release , Thyroid Neoplasms/etiology , Transcription Factors/genetics , Adult , Aged , Carcinoma, Papillary/epidemiology , Child , France/epidemiology , Gene Rearrangement , Humans , Middle Aged , Neoplasms, Radiation-Induced/epidemiology , Nuclear Receptor Coactivators , Oncogene Proteins, Fusion , Protein-Tyrosine Kinases , Thyroid Neoplasms/epidemiology , Ukraine/epidemiology
16.
Br J Surg ; 92(4): 449-53, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15672437

ABSTRACT

BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare disease, with variable tendency to lymphatic spread. The aim of this retrospective study was to identify distinctive features of large MTC with and without nodal metastases. METHODS: Between 1993 and 2003, 28 consecutive patients underwent total thyroidectomy and neck node dissection for sporadic MTC larger than 10 mm in diameter. RESULTS: All tumours were confirmed to be malignant with a locally invasive pattern of growth. Lymph node metastases were present in 16 patients (N1) and absent in 12 (N0). There were no statistically significant differences between patients with N0 and N1 tumours concerning age (mean 52.1 versus 53.4 years), male:female ratio (0.7 versus 1.0), basal preoperative calcitonin concentration (mean 3238 versus 3076 pg/ml) and tumour size (23.3 versus 23.9 mm). There were differences in the incidence of tumour invasion (P < 0.001), vascular embolism (P = 0.011) and peritumoral thyroiditis (P = 0.039). Measurement of basal and stimulated calcitonin levels after surgery confirmed biochemical cure in all patients with N0 tumours and half of those with N1 disease (P = 0.006). CONCLUSION: There were no preoperative factors that predicted node status for MTC larger than 1 cm in this series. Total thyroidectomy and nodal dissection remains the optimal treatment.


Subject(s)
Carcinoma, Medullary/secondary , Thyroid Neoplasms/pathology , Adolescent , Adult , Aged , Carcinoma, Medullary/surgery , Female , Humans , Lymphatic Metastasis/pathology , Male , Middle Aged , Preoperative Care , Remission Induction , Retrospective Studies , Thyroid Neoplasms/surgery , Thyroidectomy/methods , Thyroiditis/pathology
17.
J Med Genet ; 41(3): 161-70, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14985374

ABSTRACT

INTRODUCTION: Akt activation is involved in the pathogenesis of inherited thyroid cancer in Cowden's syndrome and in sporadic thyroid cancers. In cell culture, Akt regulates thyroid cell growth and survival; but recent data suggest that Akt also regulates cell motility in non-thyroid cell lines. We therefore sought to evaluate the role of Akt in thyroid cancer progression. METHODS: We evaluated 46 thyroid cancer, 20 thyroid follicular adenoma, and adjacent normal tissues samples by immunohistochemistry for activated Akt (pAkt), Akt 1, 2, and 3, and p27 expression. Immunoblots were performed in 14 samples. RESULTS: Akt activation was identified in 10/10 follicular cancers, 26/26 papillary cancers, and 2/10 follicular variant of papillary cancers, but in only 4/66 normal tissue samples and 2/10 typical benign follicular adenomas. Immunoactive pAkt was greatest in regions of capsular invasion; and was localised to the nucleus in follicular cancers and the cytoplasm in papillary cancers, except for invasive regions of papillary cancers where it localised to both compartments. Immunoactive Akt 1, but not Akt 2 or Akt 3, correlated with pAkt localisation, and nuclear pAkt was associated with cytoplasmic expression of p27. In vitro studies using human thyroid cancer cells demonstrated that nuclear translocation of Akt 1 and pAkt were associated with cytoplasmic p27 and cell invasion and migration. Cell migration and the localisation of Akt 1, pAkt, and p27 were inhibited by PI3 kinase, but not MEK inhibition. DISCUSSION: These data suggest an important role for nuclear activation of Akt 1 in thyroid cancer progression.


Subject(s)
Proto-Oncogene Proteins , Retroviridae Proteins, Oncogenic/metabolism , Thyroid Neoplasms/enzymology , Thyroid Neoplasms/pathology , Adenoma/enzymology , Adenoma/genetics , Adenoma/pathology , Cell Cycle Proteins/metabolism , Cell Movement , Cell Nucleus/enzymology , Cell Nucleus/metabolism , Cyclin-Dependent Kinase Inhibitor p27 , Cytoplasm/enzymology , Disease Progression , Enzyme Activation , Humans , Immunohistochemistry , Isoenzymes/metabolism , Neoplasm Invasiveness , Oncogene Protein v-akt , Phosphatidylinositol 3-Kinases/metabolism , Protein Serine-Threonine Kinases/metabolism , Protein Transport , Proto-Oncogene Proteins c-akt , Thyroid Gland/cytology , Thyroid Gland/enzymology , Thyroid Gland/metabolism , Thyroid Gland/pathology , Thyroid Neoplasms/genetics , Tumor Suppressor Proteins/metabolism
18.
J Clin Endocrinol Metab ; 88(6): 2745-52, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12788883

ABSTRACT

The prevalence of H-RAS, K-RAS, and N-RAS gene mutations in thyroid tumors according to malignancy and histology is controversial. Differences in methodology and histological classifications may explain discrepant results. To address this issue, we first performed a pooled analysis of 269 mutations garnered from 39 previous studies. Mutations proved significantly less frequent when detected with direct sequencing than without (12.3% vs. 17%). The rate of mutation involving N-RAS exon 1 (N1) and K-RAS exon 2 (K2) was less than 1%. Mutations of codon 61 of N-RAS (N2) were significantly more frequent in follicular tumors (19%) than in papillary cancers (5%) and significantly more frequent in malignant (25%) than in benign (14%) tumors. H-RAS mutations in codons 12/13 (H1) were found in 2-3% of all types of tumors, but H-RAS mutations in codon 61 (H2) were observed in only 1.4% of tumors, and almost all of them were malignant. K-RAS mutations in exon 1 were found more often in papillary than follicular cancers (2.7% vs. 1.6%) and were sometimes correlated with special epidemiological circumstances. The second part of this study involved analysis of 80 follicular tumors from patients living in Marseille (France) and Kiev (Ukraine). We used direct sequencing after PCR amplification of exons 1 and 2 of the three RAS genes. Common and atypical adenomas were separated using strict cytological criteria. Mutations of H1-RAS were found in 12.5% of common adenomas and one follicular carcinoma (2.9%). Mutations of N2-RAS occurred in 23.3% and 17.6% of atypical adenomas and follicular carcinomas, respectively. These results confirm the predominance of N2-RAS mutations in thyroid follicular tumors and their correlation with malignancy. They support the implication of N2-RAS mutations in the malignant progression of thyroid follicular tumors and the assumption that some atypical adenomas are precursors of follicular carcinomas.


Subject(s)
Adenocarcinoma, Follicular/genetics , Adenoma/genetics , Genes, ras/genetics , Mutation , Thyroid Neoplasms/genetics , Adult , Aged , Female , France , Humans , Male , Middle Aged , Ukraine
20.
J Pathol ; 194(2): 183-93, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11400147

ABSTRACT

Despite several recent studies, the biological status and clinical relevance of telomerase expression in tumours derived from the thyroid follicular cell remain controversial. This study has analysed a series of normal, benign, and malignant thyroid samples using two novel approaches: the use of purified epithelial cell fractions to eliminate false-positives due to telomerase-positive infiltrating lymphocytes; and the simultaneous measurement of telomere length to provide a clearer interpretation of telomere dynamics in thyroid neoplasia. The data obtained support the prediction that the epithelial component of non-neoplastic thyroid and of follicular adenomas is telomerase-negative, any positive results being explicable by lymphocyte infiltration. In contrast, many malignant tumours, both follicular and papillary, were telomerase-positive. However, serial dilution of extracts indicated a wide spectrum of activity in these cancers, possibly related to variation in the proportion of telomerase-positive cells. Furthermore, an unexpectedly high proportion were telomerase-negative, a finding which was not explicable by technical problems such as TRAP (telomeric repeat amplification protocol) assay sensitivity. Many of these apparently telomerase-negative tumours had abnormally long telomeres. Correlation of telomerase and telomere length data suggests that thyroid cancers fall into three biological groups: telomerase-positive lesions, consistent with the conventional model of telomere erosion followed by telomerase reactivation; telomerase-negative tumours, which maintain telomere length by a mechanism independent of telomerase; and telomerase-negative tumours which are still undergoing telomere erosion and may therefore be composed of mortal cancer cells. From a clinical standpoint, it is concluded that telomerase detection on unfractionated tissue, such as fine needle aspirates, is of no value as a marker of malignancy in follicular lesions, due to both low sensitivity and specificity.


Subject(s)
Clinical Enzyme Tests , Telomerase/analysis , Telomere/ultrastructure , Thyroid Neoplasms/diagnosis , Adenoma/diagnosis , Adult , Biopsy, Needle , Carcinoma, Papillary/diagnosis , Carcinoma, Papillary, Follicular/diagnosis , Cytogenetic Analysis , Female , Goiter, Nodular/enzymology , Graves Disease/enzymology , Humans , Male , Middle Aged , Predictive Value of Tests , Sensitivity and Specificity , Thyroid Gland/enzymology , Thyroid Neoplasms/enzymology , Thyroid Neoplasms/ultrastructure
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