Ultrasound for the detection of the pyramidal lobe of the thyroid gland.

PURPOSE: The pyramidal lobe (PL) is an ancillary lobe of the thyroid gland that can be affected by the same pathologies as the rest of the gland. We aimed to assess the diagnostic performance of high-resolution sonography in the detection of the PL with verification by dissection and histological examination. METHODS: In a prospective, cross-sectional mono-center study, 50 fresh, non-embalmed cadavers were included. Blinded ultrasound examination was performed to detect the PL by two investigators of different experience levels. If the PL was detected with ultrasound, dissection was performed to expose the PL and obtain a tissue sample. When no PL was detected with ultrasound, a tissue block of the anterior cervical region was excised. An endocrine pathologist microscopically examined all tissue samples and tissue blocks for the presence of thyroid parenchyma. RESULTS: The prevalence of the PL was 80% [40/50; 95% CI (68.9%; 91.1%)]. Diagnostic performance for both examiners was: sensitivity (85.0%; 42.5%), specificity (50.0%; 60.0%), positive predictive value (87.2%; 81.0%), negative predictive value (45.5%; 21.0%) and accuracy (78.0%; 46.0%). Regression analysis demonstrated that neither thyroid parenchyma echogenicity, thyroid gland volume, age nor body size proved to be covariates in the accurate detection of a PL (p > .05). CONCLUSION: We report that high-resolution ultrasound is an adequate examination modality to detect the PL. Our findings indicate a higher prevalence than previously reported. Therefore, the PL may be regarded as a regular part of the thyroid gland. We also advocate a dedicated assessment of the PL in routine thyroid ultrasound.

Omission of lateral lymph node dissection in medullary thyroid cancer without a desmoplastic stromal reaction.

BACKGROUND: Medullary thyroid cancer can be subdivided during surgery into tumours with or without a desmoplastic stromal reaction (DSR). DSR positivity is regarded as a sign of disposition to metastasize. The aim of this study was to analyse whether lateral lymph node dissection can be omitted in patients with DSR-negative tumours. METHODS: This was a retrospective cohort study of a prospectively maintained database of patients with medullary thyroid cancer treated using a standardized protocol, and subdivided into DSR-negative and -positive groups based on the results of intraoperative frozen-section analysis. Patients in the DSR-negative group did not undergo lateral lymph node dissection. Long-term clinical and biochemical follow-up data were collected, and baseline parameters and histopathological characteristics were compared between groups. RESULTS: The study included 360 patients. In the DSR-negative group (17.8 per cent of all tumours) no patient had lateral lymph node or distant metastases at diagnosis or during follow-up, and all patients were biochemically cured. In the DSR-positive group (82.2 per cent of all tumours), lymph node and distant metastases were present in 31.4 and 6.4 per cent of patients respectively. DSR-negative tumours were more often stage pT1a and were significantly smaller. The median levels of basal calcitonin and carcinoembryonic antigen were significantly lower in the DSR-negative group, although when adjusted for T category both showed widely overlapping ranges. CONCLUSION: Lymph node surgery may be individualized in medullary thyroid cancer based on intraoperative analysis of the DSR. Patients with DSR-negative tumours do not require lateral lymph node dissection.

Can quantitative diffusion-weighted MR imaging differentiate benign and malignant cold thyroid nodules? Initial results in 25 patients.

BACKGROUND AND PURPOSE: The characterization of cold nodules of the thyroid gland is mandatory because approximately 20% of these nodules are of malignant origin. The purpose of this study was to evaluate the distinction of cold thyroid nodules by using quantitative diffusion-weighted MR imaging (DWI). MATERIALS AND METHODS: In 25 patients with cold nodules on scintigraphy and suggestive findings at fine-needle aspiration, thyroid carcinoma was suggested. In these patients, cold nodules and the normal parenchyma of the contralateral thyroid lobe were prospectively investigated with quantitative DWI (echo-planar imaging sequence; maximum b-value, 800 s/mm(2)) before surgery. The differences in the mean apparent diffusion coefficient (ADC) values in benign and malignant nodules were tested by using a Mann-Whitney U test. RESULTS: Histologically, there were 20 carcinomas with a minimum size of 8 mm and 5 adenomas. The mean ADC values (in 10(-3) mm(2)/s) differed significantly among carcinoma, adenoma, and normal parenchyma (P < .05). The ranges (95% confidence interval) of the ADC values for carcinoma (2.43-3.037), adenoma (1.626-2.233), and normal parenchyma (1.253-1.602) showed no overlap. When an ADC value of 2.25 or higher was used for predicting malignancy, the highest accuracy of 88%, with 85% sensitivity and 100% specificity, was obtained. CONCLUSIONS: Quantitative DWI seems to be a feasible tool with which to differentiate thyroid carcinomas from adenomas; however, further studies are required including larger numbers of patients to confirm our results.

Sporadic hypercalcitoninemia: clinical and therapeutic consequences.

'Calcitonin screening' is not accepted as the standard of care in daily practice. The clinical and surgical consequences of 'calcitonin screening' in a series of patients with mildly elevated basal calcitonin and pentagastrin stimulated calcitonin levels are presented. 260 patients with elevated basal (>10 pg/ml) and stimulated calcitonin levels (>100 pg/ml) were enrolled in this prospective study. None of the patients was member of a known medullary thyroid carcinoma family. Thyroidectomy and bilateral central and lateral neck dissections were performed. Testing for the presence of germ-line mutations was performed in all patients. Histological and immunohistochemical findings were compared with basal and stimulated calcitonin levels. All patients were subsequently followed biochemically. C-cell hyperplasia (CCH) was found in 126 (49%) and medullary thyroid cancer was found in 134 (51%) patients. RET proto-oncogen mutations were documented in 22 (8%) patients (medullary thyroid cancer:18, CCH:4). In 56 (46%) of 122 patients, sporadic CCH was classified neoplastic ('carcinoma in situ'). Of 97 (72%; 10 with hereditary medullary thyroid cancer) had pT1 (International Union against Cancer recommendations 2002) and 33 (25%) had pT2 or pT3 and 4 (3%) pT4 tumors. Of 39 (29.1%) had lymph node metastases. 106 (79.1%; 15 (38.5%) with lymph node metastases) patients were cured. Evaluation of basal and stimulated calcitonin levels enables the prediction of medullary thyroid cancer. All patients with basal calcitonin >64 pg/ml and stimulated calcitonin >560 pg/ml have medullary thyroid cancer. Medullary thyroid cancer was documented in 20% of patients with basal calcitonin >10 pg/ml but <64 pg/ml and stimulated calcitonin >100 pg/ml but <560 pg/ml.

Desmoplasia in medullary thyroid carcinoma: a reliable indicator of metastatic potential.

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.

Calcitonin concentrations in patients with chronic kidney disease and medullary thyroid carcinoma or c-cell hyperplasia.

It is currently not known which level of pentagastrin-stimulated calcitonin serum concentration indicates medullary thyroid carcinoma in patients with chronic kidney disease (CKD). We examined CKD stage 3-5 patients who had total thyroidectomy because of a pentagastrin-stimulated calcitonin concentration greater than 100 pg/ml, and tested the diagnostic performance of basal and pentagastrin-stimulated calcitonin levels for differentiating medullary thyroid carcinoma and C-cell hyperplasia in this patient population. A total of 180 CKD patients presented with an elevated calcitonin level and had a pentagastrin stimulation test. Forty patients showed a maximum pentagastrin-stimulated calcitonin concentration greater than 100 pg/ml, and 22 patients had a total thyroidectomy. Seven of these 22 patients presented with a medullary thyroid carcinoma, all other patients showed C-cell hyperplasia. Patients with medullary thyroid carcinoma showed higher unstimulated (212 pg/ml (36-577) vs 42 pg/ml (17-150); P < 0.001) and higher maximum pentagastrin-stimulated calcitonin concentrations (862 pg/ml (431-2423) vs 141 pg/ml (102-471); P < 0.001) as compared to patients with C-cell hyperplasia. The sensitivity (100%) and specificity (93%) estimates suggested that a maximum pentagastrin-stimulated calcitonin concentration greater than 400 pg/ml indicates the presence of medullary thyroid carcinoma in patients with CKD. Receiver-operating characteristic (ROC) analysis revealed an area under the ROC plot of 0.99 for maximum pentagastrin-stimulated calcitonin concentrations. A maximum pentagastrin-stimulated calcitonin concentration greater than 400 pg/ml appears to be a clinically meaningful threshold for thyroidectomy.

Jun and Fos family protein expression in human breast cancer: correlation of protein expression and clinicopathological parameters.

OBJECTIVES: The activator protein-1 (AP-1) is a dimeric transcription factor formed by members of the Jun and Fos protein family. AP-1 plays a role in a variety of physiological functions including cell proliferation and differentiation, although both c-Jun and c-Fos have also been implicated in oncogenic transformation and tumor progression. To further elucidate the role of AP-1 in breast cancer, we have investigated the expression of the AP-1 proteins c-Jun, JunB, JunD, phosphorylated c-Jun, c-Fos, Fral, Fra2 and the tumor supressor protein p53. METHODS: Protein expression was evaluated on a breast cancer tissue microarray with 58 lymph node positive or negative breast cancer specimens, 29 corresponding lymph node metastases, and 11 tissue samples from surrounding tumor-free tissue, each cored as triplicate. Jun and Fos protein family expression was evaluated by immunohistochemistry and was correlated with clinicopathological parameters. RESULTS: High expression levels were observed for c-Jun, JunD, c-Fos and Fra2, whereas JunB and Fral exhibited lower staining. c-Jun protein expression was correlated to Fral staining (p = 0.007, Kendall's Tau) and Fral was further associated with c-Fos (p < 0.001), JunD (p = 0.001) and Fra2 (p = 0.011) expression. JunD expression correlated with c-Fos (p < 0.001), JunB (p = 0.035) and c-Jun (p = 0.05). Activated c-Jun correlated with c-Fos expression (p = 0.041). JunB was negatively correlated to tumor stage, (p = 0.093, corr coeff. = -0.293, Spearman's correlation) but was significantly increased in nodal negative tumors (p = 0.004, Mann Whitney test). In addition, increased Fral expression showed a trend towards an increased overall survival (p = 0.077, RR = 0.534, Cox regression). CONCLUSION: Our results suggest an important role for JunB and Fral in the biological behavior of malignant breast tumors.

Early diagnosis and curative therapy of medullary thyroid carcinoma by routine measurement of serum calcitonin in patients with thyroid disorders.

To identify patients with medullary thyroid carcinoma (MTC) at a potentially curable stage of the disease, serum concentrations of calcitonin (hCT) were determined in 14,000 patients (including 10,158 patients with thyroid nodules) referred to a thyroid outpatient clinic. Excluding patients in whom elevated basal hCT concentrations had already been known at the time of their referral, 507 patients with thyroid nodules presented basal concentrations of hCT of more than 10 pg/ml. Following stimulation by IV pentagastrin (0.5 microg/kg BW), hCT concentrations of more than 100 pg/ml were seen in 103 patients. This group included 32 new cases of MTC (29 patients with sporadic MTC and 3 new index cases of the familial form) and 43 patients with C cell hyperplasia (CCH). Among the 3,843 patients without thyroid nodules, 2 were found to harbor sporadic MTC while 4 had CCH. As compared to 1.1 cases of MTC per 1,000 patients with nodular thyroid diseases diagnosed in our institution before hCT screening was begun, 3.2 cases of MTC per 1,000 patients were identified when hCT was determined in all patients with thyroid nodules. The determination of hCT in all patients with thyroid nodular disease facilitates the timely diagnosis of MTC, thus providing the chance of curative surgery.

Primary hyperparathyroidism as the leading symptom in a patient with a Y791F RET mutation.

Primary hyperparathyroidism (PHP; serum calcium 2.75 mmol/L, PTH 226 pg/ml) had been the first clinical manifestation of MEN-2A in a female patient (aged 55 years) with a mutation (Y791F, TAT-->TTT) in exon 13 of the RET proto-oncogene. The patient has a pentagastrin-induced rise in serum calcitonin (up to 57 pg/ml) considered normal for noncarriers but abnormal in family members of MEN-2 patients. This is the first case of MEN-2 due to this specific mutation with primary hyperparathyroidism as the first manifestation of the disease. In addition, the patient harbored, within the Menin gene, a polymorphism (D418D) reportedly associated with sporadic primary hyperparathyroidism. This case report indicates that molecular biological tests in MEN- 2 may only suggest a certain phenotype but cannot predict it with certainty. It may also suggest that genetic screening for MEN-2 may be advisable in patients with primary hyperparathyroidism and a borderline-high pentagastrin stimulation test, even in the absence of a positive family history.

Polymorphisms in exon 13 and intron 14 of the RET protooncogene: genetic modifiers of medullary thyroid carcinoma?

CONTEXT: Single-nucleotide polymorphisms (SNPs) of the RET protooncogene (RET) could modify disease susceptibility and clinical phenotype in patients with sporadic or familial medullary thyroid carcinoma (FMTC). OBJECTIVE/DESIGN OF THE STUDY: Because frequencies of RET SNPs have not yet been evaluated in patients with elevated serum concentrations of calcitonin (hCt), a biochemical marker for medullary thyroid carcinoma (MTC), we studied RET SNPs in patients with FMTC (n = 22), patients with sporadic MTC (n = 45), and 71 subjects presenting with moderately elevated hCt concentrations (basal, >10 pg/ml; pentagastrin stimulated, > 50 < 100 pg/ml) in comparison with an age- and gender-matched control group (n = 79) with basal hCt concentrations in the normal range (<5 pg/ml). METHODS: After DNA extraction from citrated whole blood, RET exons 10, 11, 13, 14, 15, and 16 and exon/intron boundaries were analyzed by PCR-based cycle sequencing for RET germ line mutations, exonic (G691S, L769L, S836S, S904S) and intronic (IVS13+158; NCBI rs2472737 = IVS14-24) SNPs. RESULTS: In FMTC patients, the F791Y mutation was found to be associated (P = 0.001) with the L769L SNP. The exonic SNPs (G691S, L769L, S836S, and S904S) were not different among the four groups. The intron 14 SNP (IVS14-24), however, was more frequent in individuals with elevated hCt serum concentrations (P = 0.016) and patients with sporadic MTC (P < 0.001) when compared with the control group. CONCLUSIONS: These data suggest that the exon 13 (L769L) and the intron 14 (IVS14-24) SNPs could act as genetic modifiers in the development of some forms of hereditary and sporadic MTC, respectively.

Importance of tumour size in papillary and follicular thyroid cancer.

BACKGROUND: The most controversial change in the new pathological tumour node metastasis (pTNM) classification of thyroid tumours is the extension of the pT1 classification to include tumours up to 20 mm. METHODS: Four hundred and three patients with pT1 or pT2 differentiated thyroid carcinomas were divided into three groups according to tumour diameter (group 1, 10 mm or less; group 2, 11-20 mm; group 3, 21-40 mm). They were analysed retrospectively with respect to carcinoma-specific and disease-free survival. RESULTS: No patient in group 1 died from papillary thyroid carcinoma, compared with three patients in group 2 and six in group 3. There was a statistically significant difference in carcinoma-specific survival between groups 1 and 2 (P = 0.033). Two patients in group 1, six in group 2 and eight in group 3 developed recurrence. The difference in disease-free survival between groups 1 and 2 was significant (P = 0.025). One patient in group 1, three in group 2 and four in group 3 died from follicular thyroid carcinoma, but there were no significant differences in survival between the three groups. CONCLUSION: Extension of the pT1 classification to cover all tumours up to 20 mm does not appear to be justified for papillary thyroid carcinoma.

Prognostic factors of papillary and follicular thyroid cancer: differences in an iodine-replete endemic goiter region.

Papillary (PTC) and follicular thyroid carcinoma (FTC) are known as differentiated thyroid carcinoma (DTC). Nevertheless, according to the UICC/AJCC (TNM) classification PTC and FTC are frequently analyzed as one cancer. The aim of this study is to show differences in outcome and specific prognostic factors in an iodine-replete endemic goiter region. Six hundred and three patients with DTC treated within a 35-year-period were retrospectively analyzed with respect to carcinoma-specific survival. Prognostic factors were tested for their significance using univariate and multivariate analysis. The histological type (PTC versus FTC) was found to be a highly significant factor - carcinoma-specific survival both in univariate (P<0.001) and multivariate analyses (P=0.003) was significantly different. Univariate analysis revealed patients' age, extra-thyroid tumor spread, lymph node and distant metastases, increasing tumor size, and the tall cell variant to be significant prognostic factors for PTC patients. Age > or =45 years, positive lymph nodes and increasing tumor size were confirmed as independent prognostic factors. Univariate analysis of FTC patients revealed age at presentation, gender, extrathyroidal tumor spread, lymph node and distant metastases, increasing tumor size, multifocality, widely invasive tumor growth and oxyphilic variant to be factors bearing prognostic significance. The presence of distant metastases and increasing tumor size could be identified as independent prognostic factors for FTC patients. This study shows distinctive differences in prognostic factors of PTC and FTC: independent factors predicting poor prognosis are age > or =45 years, positive lymph nodes and increasing tumor size for PTC, and distant metastases and increasing tumor size for FTC. PTC and FTC patients should be analyzed and reported separately.

Nesidioblastosis in adults: a challenging cause of organic hyperinsulinism.

BACKGROUND: Nesidioblastosis in adults has been reintroduced into the differential diagnosis of organic hyperinsulinism by the description of 'noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS)'. MATERIALS AND METHODS: Pathologic specimens of all adult patients (n = 66) operated on for organic hyperinsulinism were re-examined. Five patients fulfilled the histomorphological criteria of nesidioblastosis. Retrospective review of clinical presentation, results of 72-h fasts, intravenous tolbutamide tolerance tests, pre- and intraoperative localization studies and surgical therapy was performed. RESULTS: In contrast to NIPHS, fasting tests became positive after 8-14 h. Tolbutamide tests were positive and preoperative imaging showed negative results in all patients. At first operation distal pancreatic resections were performed in three patients, resection of the pancreatic body in one patient and biopsy of the pancreatic tail in one patient. Two of three patients with recurrent disease had to be reoperated. One patient showed a coexistence of nesidioblastosis and multiple small insulinomas and is part of a kindred with autosomal dominantly inherited 'familial islet-cell adenomatosis'. CONCLUSIONS: Surgical exploration is indicated only after thorough biochemical diagnosis. An aggressive strategy for preoperative localization including selective arterial calcium stimulation testing seems justified. There may be a combination of nesidioblastosis and islet cell tumours. A link between beta-cell hyperplasia and progression to insulinoma based on not yet known genetic causes can be suspected.

Cells obtained from colorectal microadenomas mirror early premalignant growth patterns in vitro.

LT97, a permanent cell line consisting of epithelial cells with an early premalignant genotype was established from small colorectal polyps. LT97 cells have lost both alleles of the APC tumour suppressor gene. In addition, they carry a mutated Ki-ras oncogene, while TP53 is normal. LT97 growth characteristics are thus representative of early adenomas. They had to be passaged as multicellular aggregates indicating a dependency of survival on cell-cell contact and in accordance with their premalignant genotype were not capable of growth in soft agar. LT97 cells did express both the EGF-receptor and small amounts of TGF(alpha) establishing an autocrine growth or survival pathway. However, in spite of autocrine TGF(alpha) production, growth was strongly dependent on exogenous growth factors--mainly EGF, insulin and HGF. Inhibition of the EGF-receptor kinase induced apoptosis at an IC(50) concentration of 4 micromolar indicating that TGF(alpha) activated survival pathways in the early adenoma cell.

[Value of a structured report for the interpretation of parathyroid scintigraphy in primary essential hyperthyroidism]. / Stellenwert eines strukturierten Befundschemas zur Interpretation der Nebenschilddrüsenszintigraphie bei primärem Hyperparathyreoidismus.

The aim of the study was to evaluate whether a four-stage report scheme increases the diagnostic accuracy of dual phase Tc-99 m sestamibi scintigraphy (MIBI-scintigraphy) in patients with primary hyperparathyroidism (pHPT). We analysed the scans of 35 patients with primary hyperparathyroidism referred for Tc-99 m sestamibi scintigraphy and compared them with the sonographic and surgical findings. All scans were interpreted following a four-stage report scheme: Group A--typical scintigraphic findings of a single gland disease, group B--scan consistent with single gland disease, group C--multiple gland disease, group D--non diagnostic scan. Twenty-three scans were ranked in group A. In all these patients, scintigraphy diagnosed both the side and the localization of the adenoma correctly. Sonography made the correct diagnosis in 21/23 individuals and showed false-positive results in 2/23 cases. Group B included 10 scans. In 7/10 individuals, both the side and the localization of the adenoma were diagnosed correctly, whereas in 2/10 patients only the side was diagnosed. The scan of a single patient with hyperplasia of all 4 parathyroid glands was falsely interpreted as "consistent with a left caudal single gland disease". Sonography made the correct diagnosis in 8/10 cases, two individuals were diagnosed as false positive and false negative, respectively. No scan was interpreted as multiple gland disease (group C) and two scans were non diagnostic (group D). Both patients of the last group were correctly diagnosed by sonography. These findings suggest that in case of typical scintigraphic findings of single gland disease, scintigraphy but not sonography should be the primary localization technique for minimally invasive parathyroidectomy.

Sporadic versus familial medullary thyroid microcarcinoma: a histopathologic study of 50 consecutive patients.

By means of calcitonin screening programs, sporadic and hereditary medullary thyroid carcinoma (MTC) can be detected at an early stage. We investigated the histopathologic findings of 16 familial (mean age 32 +/- 21 years, female/male ratio 1.6:1) and 34 sporadic (mean age 58 +/- 15 years; female/male ratio 2.4:1) MTCs with stage T1 comparatively. Patients with hereditary tumors were younger. Hereditary tumors were more often found multifocal (13 of 16 vs 3 of 34; p < 0.001), bilateral (11 of 16 vs 3 of 34; p < 0.001), displaying desmoplastic stroma (14 of 16 vs 19 of 34; p = 0.02), and accompanied by C cell hyperplasia (16 of 16 vs 24 of 34; p = 0.01), but all of these factors were present in some sporadic patients. Only tumors with desmoplastic stroma showed lymph node metastasis, which was observed in eight of the 50 patients. After surgery all patients showed permanent normalization of calcitonin levels. We conclude that 1) morphologic parameters considered to indicate familial MTC risk are of no value in the individual patient, 2) many sporadic MTCs develop on the background of CCH, 3) tumors with desmoplastic stroma are more likely to develop lymph node metastasis, and 4) early detection of MTC permits curative surgery in the majority of patients.

Latent carcinoma of the thyroid in Austria: a systematic autopsy study.

Data concerning the incidence of latent thyroid carcinoma (LTC) in populations with endemic goiter are scarce. Despite the introduction of iodine goiter prophylaxis in the early sixties, iodine supply is still insufficient in Austria and goiter remains endemic. This is the first detailed study dealing with epidemiological features of LTC at autopsy in Austria. A total of 118 thyroid glands were included in the study. The glands were serially sectioned at 2- to 3-mm intervals, embedded in paraffin and histologically examined for the presence of LTC. In addition, the incidence and severity of lymphocytic thyroiditis (LT) were evaluated. Ten thyroids were found to contain LTC (8.6%). All were of the papillary type. The mean tumor dimension was 4.9 mm +/- 3.2, the smallest lesion measuring 1 mm. Only the largest tumor slightly exceeded the extent of a microcarcinoma and measured 10.5 mm. Multifocal disease was present in three cases (30%). The prevalence of latent papillary thyroid carcinoma (LPTC) was 6.6% (n = 4) in females and 10.5% (n = 6) in males. The mean age of the subjects with LPTC was 67.7 +/- 14.4 yr, range 37 to 77 yr. Goitrous thyroids were seen in 33 cases (28%): One gland was diffusely enlarged and 32 (27.1%) enlarged glands were nodular goiters. The overall prevalence of LT was 30.5% (n = 36) and the only type of thyroiditis observed was focal lymphocytic thyroiditis (FLT). There was no correlation between the presence of LPTC and goiter, the presence of FLT and the subjects' age and sex. The incidence of LPTC in Austria is similar to that in nongoitrous regions. The adult population at large seems to be uniformly exposed to factors involved in the initiation and early growth of papillary thyroid carcinoma (PTC). This suggests that the levels of iodine intake only play a minor role in the early phase of the carcinogenesis of PTC, but may be of some importance in the progression of LPTC to clinically evident PTC.

FDG positron emission tomographic, radioiodine, and MIBI imaging in a patient with poorly differentiated insular thyroid carcinoma.

Poorly differentiated insular thyroid carcinoma is now classified as a separate entity among other tumors of the thyroid gland. Its histologic pattern and its clinical course are regarded as intermediate between well differentiated and anaplastic thyroid cancer. Insular carcinoma accumulates I-131, but no data exist regarding its fluorodeoxyglucose (FDG) positron emission tomographic (PET) uptake. The authors report F-18 FDG PET, Tc-99m MIBI, and radioiodine imaging features in a 63-year-old patient with metastatic insular thyroid carcinoma. After total thyroidectomy (for poorly differentiated insular carcinoma pT3a), the patient was referred for radioiodine ablation. No signs of recurrence were present until 16 months later, when thyroglobulin levels increased. An I-131 scan showed a single lesion in the right lung, and further radioiodine treatment was administered (cumulative dose [530 mCi], 19,610 MBq I-131). Three years after the initial diagnosis, FDG-PET and Tc-99m MIBI scans were performed within 5 days during thyroxine treatment. After that, thyroxine substitution was withdrawn; 6 weeks later, an I-131 whole-body scan was performed. Both radioiodine and MIBI images showed increased tracer uptake in the known lung lesion. However, FDG PET showed a normal tracer distribution. Magnetic resonance and computed tomographic imaging confirmed a 12-mm lesion in the right upper lobe. These findings support the concept of the "flip-flop phenomenon" in insular thyroid carcinoma, an alternating pattern of metastases with either I-131 or FDG-uptake. Despite poorly differentiated histologic findings, glucose metabolism was not increased in this patient with an insular tumor.

Characterization of (123)I-vascular endothelial growth factor-binding sites expressed on human tumour cells: possible implication for tumour scintigraphy.

To explore the possibility of vascular endothelial growth factor (VEGF) receptor scintigraphy of primary tumours and their metastases, we analysed the binding properties of (123)I-labelled VEGF(165) ((123)I-VEGF(165)) and (123)I-VEGF(121) to human umbilical vein endothelial cells (HUVECs), several human tumour cell lines (HMC-1, A431, KU812, U937, HEP-1, HEP-G2, HEP-3B and Raji), a variety of primary human tumours (n = 40) and some adjacent non-neoplastic tissues as well as normal human peripheral blood cells in vitro. Two classes of high-affinity (123)I-VEGF(165)-binding site were found on the cell surface of HUVECs. In contrast, one class of high-affinity binding sites for (123)I-VEGF(165) was found on HMC-1, A431, HEP-1, HEP-G2, HEP-3B and U937 cells as well as many primary tumours. For (123)I-VEGF(121), a single class of high-affinity binding site was found on certain cell lines (HUVEC, HEP-1 and HMC-1) and distinct primary tumours (primary melanomas, ductal breast cancers and ovarian carcinomas as well as meningiomas). Tumour cells expressed significantly higher numbers of VEGF receptors compared with normal peripheral blood cells and adjacent non-neoplastic tissues. Immunohistochemical staining revealed that the VEGF receptor Flk-1 is expressed to a much higher extent within malignant tissues compared with neighbouring non-neoplastic cells. We observed significantly greater specific binding of (123)I-VEGF(165) and (123)I-VEGF(121) to a variety of human tumour cells/tissues compared with the corresponding normal tissues or normal peripheral blood cells. In comparison with (123)I-VEGF(121), (123)I-VEGF(165) bound to a higher number of different tumour cell types with a higher capacity. Thus, (123)I-VEGF(165) may be a potentially useful tracer for in vivo imaging of solid tumours.

Treatment of gastric neuroendocrine tumors: the necessity of a type-adapted treatment.

BACKGROUND: Gastric neuroendocrine (or gastric carcinoid) tumors have recently been classified into 3 types that differ in biological behavior and prognosis. Although the necessity of type-adapted treatment is widely accepted, it seems inconsistently used in daily practice. HYPOTHESIS: Diagnostic differentiation into various biological types is necessary for an adequate treatment of gastric neuroendocrine tumors. DESIGN: Retrospective study. SETTING: University hospital department of surgery. PATIENTS: Twenty-seven patients with a histologically verified gastric neuroendocrine tumor. MAIN OUTCOME MEASURES: A univariate analysis of survival rates with respect to tumor type, tumor biological parameters, and treatment performed was accomplished by applying the Kaplan-Meier estimation method. The log-rank test was used to evaluate the level of significance. RESULTS: The 16 type 1 (59%) and 11 type 3 (41%) gastric neuroendocrine tumors differ in tumor size, histopathologic characteristics, and biological behavior. Nine (56%) of 16 type 1 gastric neuroendocrine tumors were treated by local excision, 8 of these (89%) had persistent atrophic gastropathy during the follow-up period. Five-year cumulative survival of patients with type 1 gastric neuroendocrine tumor was 100% without any progression into malignant phenotype. In contrast, 4 (44%) of 9 locally advanced type 3 gastric neuroendocrine tumors were treated radically by extended resection with a 5-year cumulative survival of 75%. CONCLUSIONS: Differentiation into 3 biologically distinct tumor types for gastric neuroendocrine tumors is important with respect to therapeutic strategy and prognostic consideration. Correct diagnosis is attainable by using endoscopy, histopathologic characteristics, and laboratory chemical analysis and should precede any treatment. Extended radical surgery of high-risk type 3 tumors is indicated when definitive healing is achievable, whereas type 1 tumors are best treated by endoscopic removal and long-term follow-up.