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The aim of this study was to evaluate the clinical use of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in medullary thyroid cancer (MTC) on the basis of comparison with findings obtained using indium-111 pentetreotide (SMS), pentavalent technetium-99m dimercaptosuccinic acid (DMSA), technetium-99m sestamibi (MIBI), computed tomography (CT) and magnetic resonance imaging (MRI). One hundred FDG-PET examinations in 85 patients (40 males, 45 females) with elevated tumour marker levels and/or pathological findings on other imaging methods were evaluated retrospectively. Eighty-two patients were examined after total thyroidectomy, and the remaining three patients prior to surgery. Overall, 181 lesions could be identified with at least one of the imaging techniques. Fifty-five lesions were confirmed histologically. FDG-PET detected 123 of 181 sites, which is a lesion detection probability of 68%. In the 55 cases with histological confirmation, we found 32 true positive, 3 false positive, 11 true negative and 9 false negative lesions using FDG-PET, resulting in a sensitivity of 78% and a specificity of 79%. Sensitivity and specificity were, respectively, 25% and 92% for SMS, 33% and 78% for DMSA, 25% and 100% for MIBI, 50% and 20% for CT and 82% and 67% for MRI. Compared with morphological techniques and functional imaging methods with single-photon emitters, FDG-PET showed the highest lesion detection probability for MTC tissue, with a high sensitivity and specificity. It is concluded that FDG-PET is a useful method in the staging and follow-up of MTC.

We report the case of a MEN 2a patient with a history of medullary thyroid cancer (MTC) treated by total thyroidectomy, who presented an increasing calcitonin level, suggesting tumor recurrence. Conventional radiographic and radionuclide imaging failed to localize the responsible lesions. A planar and tomographic (SPECT) [99mTc]MIBI scan, performed in order to investigate a recent hyperparathyroidism localized a parathyroid adenoma and revealed an abnormal uptake in the left lateral neck region, corresponding to apparently banal lymph nodes on MRI. This abnormal uptake was also observed on a [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) study and was proven to be an uptake in MTC lymph nodes metastases as confirmed by histopathologic analysis. We conclude that, using an adequate acquisition protocol (i.e. SPECT), [99mTc]MIBI scan is potentially able to localize both parathyroid adenoma and recurrent MTC at one and the same time, particularly in case of non-diagnostic conventional imaging techniques. In this setting, the potential usefulness of FDG-PET is also discussed.

We report a case of Sipple's syndrome with a hepatic tumor. A 28-year-old male with medullary thyroid cancer and bilateral pheochromocytomas was diagnosed as having Sipple's syndrome. The hepatic tumor was found to be hypervascular by means of a dynamic abdominal CT scan. An I-131-MIBG scan showed no increased accumulation in the tumor. A whole body Tc-99m-MIBI scan had shown, however, increased accumulation in the tumor by 10 minutes after i.v. Tc-99m-MIBI. The hepatic tumor was diagnosed histologically as a metastasis from the medullary thyroid cancer. To our knowledge, there have been no previous reports of increased Tc-99m-MIBI accumulation in hepatic metastases from medullary thyroid cancer.

Background: Renal medullary carcinoma is a recently described, highly aggressive neoplasm that affects predominantly young African American males with a history of sickle cell trait. To the best of our knowledge, this is the first report of fine needle aspirate cytology (FNAC) findings of renal medullary carcinoma., Case: A 14-year-old, African American male with a history of sickle cell trait presented with the sudden onset of third cranial nerve palsy. Radiographic examination demonstrated possible tumor masses in the brain, thorax and left kidney. Ultrasound-guided fine needle aspiration was performed on the left kidney, and a cytologic diagnosis of "suspect renal medullary carcinoma" was rendered. The cytologic diagnosis was confirmed by tissue examination., Conclusion: The cytologic features of renal medullary carcinoma include loosely cohesive clusters and single epithelioid cells with cytologic atypia, including high nuclear/cytoplasmic ratios, hyperchromasia, prominent nucleoli and cytoplasmic vacuolation. These cytologic findings, coupled with clinical findings (young black male with sickle cell trait), allow recognition of this rare renal neoplasm.

Current therapeutic approaches in neuroendocrine tumours include surgery, radiotherapy and polychemotherapy. Different metabolic patterns of neuroendocrine tumours allow the use of a wide range of diagnostic options in nuclear medicine, due to the presence of a wide spectrum of radiotracers electively concentrating in these neoplasms. Nuclear medicine, and in particular 111In Octreotide (OCT) scintigraphy, 123I Methaiodobenzylguanidine (MIBG) and pentavalent 99mTc-DMSA (V-DMSA), together with biohumoral markers, are currently able to locate tumours also not detectable using traditional diagnostic techniques. Somatostatin analogs, such as octreotide have become increasingly important over the years in the treatment of patients with neuroendocrine tumours. At present the therapeutic use of somatostatin analogs can be schematised as 1) pharmacological treatment (with cold octreotide); 2) surgical treatment (radioguided surgery); 3) radiometabolic treatment (with marked octreotide). The development of new synthetic molecules and new radiocompounds will probably open up interesting scenarios in the near future.

Purpose: In this retrospective study, the authors evaluated the utility of In-111 octreotide (OctreoScan) and Tc-99m (V) DMSA scintigraphy for the localization of recurrent metastatic tumor foci in patients with medullary thyroid cancer (MTC) and compared the findings with those of conventional radiologic imaging methods., Methods: The scintigraphic images were compared with computed tomography (CT) and magnetic resonance imaging (MRI) and ultrasonography (US) in 14 patients (8 men, 6 women; age range, 22 to 74 years) with elevated calcitonin and carcinoembryonic antigen levels after total thyroidectomy. All scintigraphic image findings were evaluated qualitatively as mild uptake (+) and moderate to marked uptake (++)., Results: In-111 octreotide may be superior to Tc-99m (V) DMSA for the detection of tumor foci of patients with MTC on a patient basis (78.5% versus 57.1%) and on a lesion basis (44.1% versus 30.2%). The sensitivity rate for In-111 octreotide (78.5%) was also similar to that of CT and MRI on a patient basis. Conversely, the combined use of Tc-99m (V) DMSA and In-111 octreotide revealed the best sensitivity rate (85.7%) on a patient basis, whereas the combined use of CT and MRI showed the best sensitivity rate (81.3%) on a lesion basis., Conclusions: These findings suggest that In-111 octreotide is superior to Tc-99m (V) DMSA and has a similar sensitivity rate to CT and MRI for the diagnosis of recurrent or metastatic MTC. Although the combined use of In-111 octreotide and Tc-99m (V) DMSA was most sensitive, the combined use of CT and MRI with radionuclide imaging methods may better detect more metastatic tumor foci.

Background: The objective of this study was to appraise the detection of metastases of medullary thyroid carcinoma (MTC) and pheochromocytoma using radioguided surgery (RGS) and to compare the results with external imaging modalities, surgical palpation, and histopathologic findings., Methods: Twenty-five patients with recurrent MTC underwent preoperative scintigraphic imaging with 500 megabecquerels (MBq) of technetium 99m(V)-dimercaptosuccinic acid [(99m)Tc(V)-DMSA] and 222 MBq of indium 111 ((111)In)-pentetreotide. The radiopharmaceutical that showed the greatest preoperative tumor uptake was selected for intraoperative RGS. Surgery was performed 24 hours after the administration of (111)In-pentetreotide or 4 hours after the injection of (99m)Tc(V)-DMSA. Furthermore, three male patients underwent surgery who suffered from recurrent pheochromocytoma (injection of 180 MBq iodine 123-labeled metaiodobenzylguanidine [(123)I-MIBG] 4--5 hours before surgery)., Results: Overall, lesion detection sensitivities in patients with MTC for computed tomography, (111)In-pentetreotide, and (99m)Tc(V)-DMSA were 32%, 34%, and 65%, respectively. Surgical palpation identified lymph node metastases of recurrent MTC with a sensitivity of 65%, whereas RGS localized 64 malignant lesions (sensitivity, 97%). Altogether, 71 lesions could be excised, 5 of which were adjudged false positive with respect to MTC metastases. Both surgical palpation and RGS localized all paravertebral subdiaphragmatic lesions (size > or = 2 cm) of recurrent pheochromocytoma seen in the preoperative MIBG scan., Conclusions: RGS was capable of localizing more and smaller metastases of MTC compared with conventional imaging modalities and surgical palpation. However, the relatively high radioligand accumulation in the kidneys ((111)In-pentetreotide) and the dense hepatic and biliary signals using MIBG limited their use for intraoperative detection of tumors in the area of the adrenal gland., (Copyright 2001 American Cancer Society.)

Objectives: To review our experience and assess the role of TC99m MIBI thyroid scintigraphy in patients with well-differentiated thyroid carcinoma., Design: Cross sectional descriptive study comparing the results of TC99m MIBI and TC99m pertechnetate scintigraphy with histology., Setting: Ga-Rankuwa Hospital, a tertiary referral centre, MEDUNSA, South Africa., Subjects: Between October 1998 and January 2000, 63 patients presenting with a single thyroid nodule were included in this study., Intervention: All patients included in the study were subjected to fine needle aspiration, thyroid function tests, TC99m pertechnetate and TC99m MIBI scintigraphy. Following surgery all specimens were sent for pathological examination., Main Outcome Measures: The outcome of the study was measured comparing the results of pre-operative TC99m MIBI and TC99m pertechnetate scintigraphy with final histology., Results: 41 of these 63 patients were found to have benign disease and 22 patients had malignant disease. In the malignant group there were 17 females and five males. The age of the patients ranged from 28 years to 85 years in the carcinoma group. Thirteen patients had follicular carcinoma, six patients had papillary carcinoma, two patients had Hurthle cell carcinoma and one patient had medullary carcinoma. TC99m MIBI correctly predicted malignancy in 21/22 patients in contrast with TC99m pertechnetate scintigraphy which diagnosed malignancy in 17/22 patients. The sensitivity of MIBI was 95% and its specificity was found to be 63%. The sensitivity and specificity of TC99m pertechnetate, however, was 77% and 29% respectively., Conclusion: TC99m MIBI scintigraphy can be used in association with Fine Needle Aspiration (FNA) in the pre-operative evaluation of thyroid carcinoma.

Objective: To study the pattern of multiple endocrine neoplasia type IIA (MEN IIA) and describe the clinical features and results of genetic testing and treatment in 21 members of the first reported family with MEN IIA in Qatar., Methods: After identification of the proband, we screened all her family members (21 members) with genetic testing for the RET proto-oncogene mutation. Those subjects with the mutation were further assessed for pheochromocytoma by measurement of the 24-hour urinary vanillylmandelic acid, metanephrines, and catecholamines, and those with high levels underwent a metaiodobenzylguanidine scan and adrenalectomy. The serum calcium was measured in a effort to detect hyperparathyroidism. Those family members who had the mutation and were eligible for surgical treatment underwent total thyroidectomy and central compartment dissection. In those patients with high postoperative calcitonin levels, residual disease was sought with radiologic imaging, and follow-up was done with pentagastrin stimulation tests., Results: Of the 21 family members screened, 10 had the RET proto-oncogene mutation (codon 634, TGC->GGC) (5 females and 5 males; 6 adults and 4 children). All the adults had bilateral medullary thyroid carcinoma (MTC); four of them had lymph node metastatic lesions, and one had metastatic involvement of the liver. Two adults had pheochromocytomas. Two family members were reported to have parathyroid hyperplasia, although both were normocalcemic., Conclusion: This family with MEN IIA showed classic mendelian autosomal dominant inheritance. All adult patients had MTC, two had pheochromocytomas, and two had parathyroid hyperplasia. Although one child had a high stimulated calcitonin level, the histopathologic findings were normal; another child with high stimulated calcitonin levels showed C-cell hyperplasia on histopathologic examination.

Objective: An evaluation of thallium imaging for differentiating benign from malignant lesions in clinically palpable solitary, nonfunctioning, thyroid nodules., Methods: Seventy-eight patients presenting with a clinically palpable solitary nonfunctioning thyroid nodule were imaged with 3 mCi thallium-201 with a pinhole acquisition at 20 minutes and 3 hours after injection. Thallium uptake was assessed as grade 1, less than the rest of the gland; grade 2, same as the rest of the gland; and grade 3, more than the rest of the gland. All patients underwent surgery and the histology was compared with the thallium scan results., Results: Of the 78 patients presenting with solitary thyroid nodule, 13 were malignant and 65 were benign. Twenty-four patients with benign disease showed no uptake of thallium at 3 hours (grade 1). Thirty-two patients with benign disease and 2 patients with malignant lesion had grade 2 uptake at 3 hours. Eleven patients with malignant disease and 9 with benign disease had grade 3 uptake at 3 hours., Conclusions: All malignant lesions had at least grade 2 and most had grade 3 uptake at 3 hours. All lesions with grade 1 uptake at 3 hours were benign, enabling malignancy to be excluded in one-third of cases. Thallium imaging is a useful adjunct to fine-needle cytology in evaluation of solitary thyroid nodules especially when the latter is inconclusive.

In spite of the availability of numerous procedures, diagnostic imaging of tumour manifestations in patients with medullary thyroid carcinoma and elevated calcitonin levels is often difficult. In the present study, the new procedure of fluorine-18 dihydroxyphenylalanine positron emission tomography (18F-DOPA PET) was compared with the established functional and morphological imaging methods. After evaluation of the normal distribution of 18F-DOPA, 11 patients with medullary thyroid carcinoma were examined using 18F-DOPA PET. Results of 18F-fluorodeoxyglucose (18F-FDG) PET, somatostatin receptor scintigraphy (SRS) and morphological tomographic imaging (CT/MRI) were available for all patients. All individual procedures were evaluated without reference to prior information. Data assessment for each patient was based on cooperation between experienced radiologists and specialists in nuclear medicine, who considered all the available findings (histological results, imaging, follow-up studies). This cooperation served as the gold standard against which the results of the individual procedures were evaluated. A total of 27 tumours were studied [three primary tumours (PT)/local recurrence (LR), 16 lymph node metastases (LNM) and eight organ metastases (OM)]. 18F-DOPA PET produced 17 true-positive findings (2 PT/LR, 14 LNM, 1 OM), 18F-FDG PET 12 (2 PT/LR, 7 LNM, 3 OM), SRS 14 (2 PT/LR, 8 LNM, 4 OM) and morphological imaging 22 (3 PT/LR, 11 LNM, 8 OM). The following sensitivities were calculated with respect to total tumour manifestations: 18F-DOPA PET 63%, 18F-FDG PET 44%, SRS 52%, morphological imaging 81%. Thus, the morphological imaging procedures produce the best overall sensitivity, but the specificity for PT/LR (55%) and LNM (57%) was low. With respect to lymph node staging, the best results were obtained with 18F-DOPA PET. 18F-DOPA PET is a new functional imaging procedure for medullary thyroid carcinoma that seems to provide better results than SRS and 18F-FDG PET. Moreover, the data indicate that no single procedure provides adequate diagnostic certainty. Therefore, 18F-DOPA PET is a useful supplement to morphological diagnostic imaging, improving lymph node staging and enabling a more specific diagnosis of primary tumour and local recurrence.

Several studies have shown that ultrasound guidance can serve as a valuable aid in improving the diagnostic yield of fine-needle aspiration (FNA) biopsy of thyroid nodules. In this study, we evaluated the combined impact of ultrasound-guidance, rapid on-site evaluation of FNA specimens, and different cytologic preparations (fresh and alcohol-fixed smears, Millipore filter) and staining methods (Diff-Quik and Papanicolaou stains) on the diagnostic yield of thyroid FNA. Ultrasound-guided FNA was performed on 282 patients (313 cases) between November 1997 and April 1999. The diagnostic categories included: benign (198 cases, 63.2%); indeterminate (42 cases, 13.4%); suspicious for follicular variant of papillary carcinoma (26 cases, 8.3%), malignant (32 cases, 10.1%); and nondiagnostic (15 cases, 5%). The nondiagnostic cases also included 6 cystic lesions without any solid component and 3 thyroid-bed aspirations. After excluding these, the nondiagnostic rate was only 2%. Histological follow-up was available in 77 (77/313) cases. The concordance rate between cytological and histological diagnosis was 100% in malignant, 67% in suspicious, and 56% in indeterminate cases. All cases with histologic follow-up were selected to evaluate the independent diagnostic efficacy of each aforementioned cytologic staining method. A definite diagnosis could be made solely on the basis of air-dried, Diff-Quik-stained preparations in 50 (65%), alcohol-fixed, Papanicolaou stained smears in 68 (88%), and Millipore filter preparations in 70 (91%) cases. We conclude that ultrasound-guided FNA combined with on-site evaluation and different cytologic preparations can significantly improve the diagnostic accuracy of thyroid FNA specimens., (Copyright 2000 Wiley-Liss, Inc.)

Introduction: Thyroid medullary carcinoma is usually detected in the presence of an isolated thyroid nodule or in the context of a family disease: familial thyroid medullary carcinoma or multiple endocrine neoplasia type 2A., Exegesis: Here we report a third means of detection: an unexplained rise in carcinoembryonic antigen levels after cancer surgery. In each case, the carcinoembryonic antigen increase led to the assessment of the caicitonin plasma level and to a thyroid echography being performed. Thyroid medullary carcinoma was confirmed in every case after surgery., Conclusion: Even though the association of thyroid follicular carcinoma with familial adenomatous polyposis is common, the association of thyroid medullary carcinoma with breast or colonic carcinoma remains exceptional and probably accidental. Due to the seriousness of the thyroid medullary carcinoma, it is mandatory to look for it in the event of an unexplained rise in the carcinoembryonic antigen level, by assessing the calcitonin plasma level.

Purpose: We investigated whether there was a relationship between the sonographic and histologic appearances of medullary carcinomas of the breast to determine whether sonography is helpful in the differentiation of typical and atypical medullary carcinomas., Methods: We retrospectively reviewed the histologic slides and sonograms of 20 patients who had been diagnosed with medullary carcinoma of the breast. We then classified the carcinomas as typical or atypical based on strict histologic criteria. We also evaluated the relationship between sonographic findings and the histologic reclassification., Results: Eight (40%) of the 20 medullary carcinomas were classified as typical, and 12 (60%) were classified as atypical. On sonography, a smooth outline was visualized in 6 (75%) of the 8 typical medullary carcinomas but in none of the 12 atypical carcinomas. A jagged margin was sonographically visualized in 10 (83%) of the 12 atypical carcinomas, and a focal irregularity in the margin was visualized in 2 (17%) of the 12 atypical carcinomas. Four of the typical medullary carcinomas had posterior enhancement, and 9 of the atypical medullary carcinomas showed retrotumoral shadowing. The difference in tumor-margin regularity between typical and atypical medullary carcinomas was found to be statistically significant (p < 0.001) using the 2-tailed Fisher's exact test., Conclusions: To prevent overdiagnosis of medullary carcinoma, a thorough pathologic review of the entire tumor is recommended if sonography shows a jagged margin or a margin with focal irregularity., (Copyright 2000 John Wiley & Sons, Inc.)

Unlabelled: Cholecystokinin (CCK)-B receptors have been demonstrated on a high percentage of medullary thyroid carcinomas (MTC) in vitro. After encouraging results both in vitro and in animal studies, we studied the efficacy of an octapeptide [111In-DTPA]-CCK analogue in seven patients with MTC. In four of five patients in whom serum calcitonin levels were monitored, a significant rise was found following the injection, indicating retained biological activity of the radiopeptide. In all patients there was visualization of the CCK-B receptor-positive stomach. In one of two patients with known MTC lesions, some of the lesions were visualized; in addition some lesions were visualized in one of the five other patients who had elevated serum tumour markers but negative localizing studies. Radioactivity in the presumed tumour sites was still present at 48 h p.i. The uptake in the presumed tumour sites and stomach was low. Background radioactivity dropped rapidly owing to urinary excretion. After 1 h, breakdown products of the labelled analogue predominated both in urine and in serum, and virtually no intact peptide was present., In Conclusion: (1) the CCK-B receptor-positive gastric mucosa and presumed MTC lesions could be visualized in patients using an octapeptide [111In-DTPA]-CCK analogue that is probably internalized, proving the feasibility of CCK-B receptor imaging in vivo; (2) there was a relatively low uptake of the CCK analogue in the strongly CCK receptor positive stomach, and rapid degradation of the peptide in serum.

Hypothesis: Reoperation benefits patients with locoregional, persistent, or recurrent medullary thyroid cancer (MTC). Currently available localizing studies have limited utility for detecting all foci of residual MTC., Design: A retrospective study with a mean follow-up time of 7.5 years (median, 13 years; range, 2.2-29 years)., Setting: A tertiary referral medical center., Patients: Thirty-three patients who underwent 46 reoperations for locoregional residual MTC., Results: Sixty-four percent of residual MTC was located in the lateral cervical nodes, 22% in the central cervical nodes or thyroid bed, and 14% in the anterior mediastinum (197 of 1128 nodes resected were positive for MTC). After reoperation, basal calcitonin levels were undetectable in 2 patients, reduced by greater than 50% in 10 patients, and either increased or were not reduced by greater than 50% in the remaining patients. On reoperation, one patient had a thoracic duct injury that required reexploration and ligation. Patients who had a greater than 50% decrease in calcitonin levels after reoperation were less likely to develop distant metastases compared with patients who did not have a greater than 50% decrease (P<.05). The sensitivities of magnetic resonance imaging (n = 31), computed tomographic scan (n = 16), ultrasound (n = 9), and dimercaptosuccinic acid scan (n = 3) were 91%, 86%, 88%, and 100%, respectively., Conclusions: Although reoperation in patients with residual MTC rarely results in biochemical cure, cervical reexploration is safe and in selected patients may limit MTC progression. Lateral cervical node dissection could be beneficial at the time of initial surgical treatment because of the high frequency of residual MTC in the lateral cervical nodes. Noninvasive imaging studies were helpful but far from perfect for guiding the reexploration for locoregional residual MTC.

Our preliminary experience of Somatostatin Receptor Positive Tumour Scintigraphy (SRPTS) in the management of some rare neuroendocrine tumours is highlighted. Six patients were evaluated using SRPTS. A single patient each with Zollinger-Ellison syndrome, recurrent medullary carcinoma of thyroid and Stage IV neuroblastoma. Two patients with phaeochromocytoma, and one patient with suspected insulinoma were evaluated. SRPTS was useful in three of the six patients studied i.e. patient with gastrinoma, recurrent medullary carcinoma of thyroid and metastatic neuroblastoma. SRPTS although expensive is a useful and cost-effective approach of rare endocrine tumours and it role as a first line tool in the diagnosis is discussed.

The early detection of metastases from medullary thyroid cancer (MTC) is important because the only curative therapy consists in surgical removal of all tumour tissue. There is no single sensitive diagnostic imaging modality for the localization of all metastases in patients with MTC. Therefore, in many cases several imaging modalities (e.g. ultrasonography, magnetic resonance imaging, computerized tomography and scintigraphy using pentavalent technetium-99m dimercaptosuccinic acid, thallium-201 chloride, indium-111 pentetreotide, anti-CEA antibodies or metaiodobenzylguanidine) must be performed consecutively in patients with elevated calcitonin levels until the tumour is localized. In this prospective study, we investigated the value of fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG PET) in the follow-up of patients with MTC. [18F]FDG PET examinations of the neck and the chest were performed in 20 patients with elevated calcitonin levels or sonographic abnormalities in the neck. Positive [18F]FDG findings were validated by histology, computerized tomography or selective venous catheterization. [18F]FDG PET detected tumour in 13/17 patients (nine cases were validated by histology, four by computerized tomography). Five patients showed completely negative PET scans (of these cases, one was true-negative and four false-negative). One patient with [18F]FDG accumulation in pulmonary lesions from silicosis and one patient with a neck lesion that was not subjected to histological validation had to be excluded. Considering all validated localizations, [18F]FDG PET detected 12/14 tumour manifestations in the neck, 6/7 mediastinal metastases, 2/2 pulmonary metastases and 2/2 bone metastases. In two patients with elevated calcitonin levels, no diagnostic modality was able to localize a tumour. The sensitivity of [18F]FDG PET in the follow-up of MTC was 76% (95% confidence interval 53%-94%); this is encouraging. [18F]FDG PET promises to be a valuable diagnostic method, especially for the detection of lymph node metastases, surgical resection of which can result in complete remission.

Background: Sentinel lymphonodectomy is a new method for the classification of axillary lymph nodes in breast cancer. The optimum technique for the pathological examination of sentinel lymph nodes (SLNs) is still under debate., Materials and Methods: Different histopathological techniques were evaluated in order to study their diagnostic accuracy regarding the detection of metastases in 49 SLNs of 40 breast cancer patients., Results: In single hematoxylin and eosin (HE) stained paraffin sections 18 out of 40 patients showed positive SLNs and 8 out of 40 showed positive axillary lymph nodes (ALNs). Serial sections with a spacing of 150 microns between following sections revealed an additional 4 and 5 cases with positive SLNs and ALNs, respectively. Single HE frozen sections showed 11 tumor positive SLNs among 25 patients. The ultrarapid-immunohistochemistry on single frozen sections confirmed these data and detected one additional case with isolated tumor cells in the lymph node sinus., Conclusion: Histopathological nodal staging of SLNs should include serial sections with a spacing of 150 microns between sections as well as immunohistochemistry. The ultrarapid-immunohistochemistry is a sensitive method for the detection of minimal metastatic disease in SLNs and can be applied intraoperatively.

Patients with recurrent or metastatic medullary thyroid carcinoma (MTC) were referred for pretargeted immunoscintigraphy (Affinity Enhancement System; AES) and radioimmunoguided surgery (RIGS). Data collected from 13 patients establish that whole-body AES immunoscintigraphy revealed metastases < 360 mg and RIGS detected micrometastases (5-15 mg). All tissue samples removed by the surgeon were diagnosed by histology and immunohistochemistry of calcitonin to check the accuracy of IS and RIGS results. AES immunoscintigraphy is very sensitive. Of 34 metastases or recurrences detected, 22 had escaped physical examination or conventional imaging. The accuracy of RIGS was 86%, its sensitivity 75%, and its specificity was 90% (n = 208). IS and RIGS detected occult tumors that would have escaped surgery, clearly demonstrating clinical benefit. Serum calcitonin (normal, 10 pg/ml) and carcinoembryonic antigen (normal, 5 ng/ml) of two patients were restored to normal. In patients whose tumors were discovered, progression of their disease was slowed, as evidenced by the large decrease in serum calcitonin and carcinoembryonic antigen, an important prognostic factor. Surgery was canceled in one case where IS detected distant metastases out of surgical reach. Thus, AES immunoscintigraphy and RIGS might be of valuable help for the surgical management of medullary thyroid carcinoma.

Phase III clinical study was performed to evaluate clinical utility of 123I-MIBG in the localization of tumors in 48 patients with tumors of sympathetic and adrenomedullary origin, diagnosed or strongly suspected. Sixteen patients had pheochromocytoma, 23 had neuroblastoma, 7 had medullary carcinoma of the thyroid, and 2 had Sipple syndrome. In 3 out of 48 patients, 123I-MIBG scintigraphy was performed twice. The clinical utility of 123I-MIBG was evaluated in 50 cases. Out of 140 lesions, 123I-MIBG scintigraphy demonstrated 51 true positive, 79 true negative, 1 false positive, and 2 false negative. Seven lesions were not evaluable. Sensitivity was 96.2%, Specificity was 98.8%, and Accuracy was 97.7%. An acquisition between 4 hrs and a day after injection was adequate for tumor detection. Neither adverse reactions nor abnormal laboratory findings were noted in relation to 123I-MIBG injections. Our study indicates that 123I-MIBG is a safe and useful radiotracer for visualization and localization of tumors of sympathetic and adrenomedullary origin.

Background: Renal medullary carcinoma (RMC), an extremely rare tumour of the kidney, carries a dismal prognosis, with no reports to date of significant response to chemotherapy or radiotherapy. A case of this tumour in a male child, who showed a dramatic response to chemotherapy, is described., Procedure: A detailed histological evaluation of the tumour and cytogenetic analysis using fluorescent in situ hybridisation (FISH) was carried out. The child was treated with multiagent chemotherapy, followed by abdominal radiotherapy., Results: A detailed histopathological and immunohistochemical portrait of this tumour is described, and FISH studies confirmed the presence of a bcr/abl rearrangement. The child obtained complete radiological remission following chemotherapy, although he later relapsed and died of progressive disease despite further attempts at treatment with chemotherapy., Conclusions: Although there are no previous reports of response of this tumour to chemotherapy, this case illustrates that treatment of this disease is justified. The responses of other cases to similar drug regimens would be of interest to confirm whether the encouraging response described for this case could be reproduced. Cytogenetic analysis of other cases of RMC may clarify whether the abnormalities seen in this case are typical., (Copyright 1999 Wiley-Liss, Inc.)

Purpose: Accurate presurgical assessment of tumor size in breast cancer is important for choosing appropriate treatment. We retrospectively compared presurgical sonographic measurements of tumor size with postsurgical measurements of size and other variables., Methods: In 174 cases, tumor size was measured by sonography before surgery, and those measurements were compared with values obtained by histopathologic examination of the specimens. The histologic type and grade, the number of lesions, and the presence of an extensive intraductal component also were considered in the intramodal correlations of tumor size., Results: Sonographic measurements of tumor size correlated well with size measured after surgery (r = 0.72; 95% confidence interval, 0.64-0.78). The correlation was higher for lesions of 20 mm or less in their longest diameter than for larger lesions. The intramodal size correlation was lower for tumors with an extensive intraductal component than for tumors without an extensive intraductal component. The sonographic versus pathologic correlation of tumor size was less accurate when several lesions were present., Conclusions: Sonography is useful for presurgical assessment of tumor size in patients with breast cancer, especially for single lesions of 20 mm or less and without an extensive intraductal component., (Copyright 1999 John Wiley & Sons, Inc.)

Unlabelled: The usefulness of 111In-pentetreotide scintigraphy in the diagnosis of neuroendocrine tumors was evaluated., Material and Method: 39 patients with clinical or biochemical suspicion of neuroendocrine tumors were studied. 29 patients underwent surgery and diagnosis was confirmed by anatomopathology findings (7 mixed tumors, 6 carcinoids, 3 insulinomas, 3 pheocromocytomas, 2 glucagonomas, 2 medullary thyroid carcinomas, 1 gastrinoma and 5 metastatic lesions). In 10 patients who did not undergo surgery, the diagnostic criteria were based on a 6 month follow-up. 111In-pentetreotide scintigraphy and computed tomography (CT) were performed in all of the patients., Results: The scintigraphy correctly detected 58% of the primary tumors while the CT was positive in only 45% of the cases. Both techniques detected metastasis in 5 patients., Conclusion: 111In-pentetreotide scintigraphy is a useful technique to diagnose those tumors that have somatostatin receptors. In our series, the sensitivity of this method was higher than the CT.

Purpose: This prospective study assessed the detectability of metastatic lesions by Tc-99m tetrofosmin in medullary thyroid carcinoma and to compare the results with Tc-99m penta dimercapto succinic acid (VDMSA) and TI-201., Methods: A prospective study was performed on 24 patients (10 men, 14 women; ages 23 to 76 years) with medullary thyroid carcinoma after total thyroidectomy. Five cases were sporadic and 19 were familial. After the injection of 740 MBq (20 mCi) tetrofosmin, 740 MBq (20 mCi) VDMSA and 74 MBq (20 mCi) TI-201, whole-body scans and 5-minute static images of the head, neck, chest, abdomen and pelvis were obtained. All scintigraphic studies were compared with calcitonin levels, radiologic findings, histopathologic results, and clinical follow-up., Results: Thirty-four metastatic sites were detected in 12 patients on the basis clinical, radiologic, and histopathologic findings. Patients were divided into three groups according to the calcitonin levels and scintigraphic findings. Group 1 consisted of patients with elevated calcitonin levels and positive scintigraphic findings. Among 34 metastatic sites, 30 could be detected with VDMSA. Only 21 and 20 metastatic sites could be visualized with TI-201 and tetrofosmin, respectively. All 30 lesions showed intense VDMSA uptake but only faint or no uptake with TI-201 and tetrofosmin. Patients in group 2 were accepted to have micrometastases. In this group, calcitonin was minimally elevated, and the results of all three scintigraphs were negative. Group 3 included patients with true-negative results. All patients had normal calcitonin levels and negative results of scintigraphic studies., Conclusions: Tetrofosmin has no role in the detection of medullary thyroid carcinoma metastases. These results show that VDMSA is clearly superior to TI-201 and tetrofosmin in the follow-up of patients with medullary thyroid carcinoma.

Serum thyroglobulin and imaging have been routinely used in the evaluation of thyroid cancer patients suspected of having metastatic or recurrent disease. A more sensitive technique capable of identifying the sites of disease not detected by current imaging methods might improve overall management. The objective in this study was to demonstrate the feasibility of using positron emission tomography (PET) for the detection of recurrent thyroid cancer. Thirty patients with a history of either papillary/follicular or medullary thyroid cancer suspected of having locally recurrent or metastatic cancer on the basis of elevated or rising blood markers were evaluated with PET. Imaging studies were performed with the radiotracer [F-18] fluorodeoxyglucose (FDG). A retrospective review of other imaging results was performed and compared to the PET results. PET was able to identify locally recurrent or metastatic papillary/follicular disease in all 24 patients studied with elevated or rising thyroglobulin. Similar results were obtained in 6 patients with medullary cancer recurrences in the presence of elevated calcitonin. In cases where follow-up data was obtainable (17/24 papillary/follicular cancers and 4/6 medullary cancers), disease was confirmed either directly by surgery and/or indirectly through changes or persistence of laboratory findings. The results support the hypothesis that in the presence of elevated blood markers indicative of recurrent thyroid cancer, PET may prove valuable as an adjunctive imaging test for identifying disease and influencing management in cases where conventional imaging fails to detect suspected disease.

We report on radiological and cytological findings from a case of medullary thyroid carcinoma (MTC) metastatizing to the liver 12 yr after the eradication of the primary neoplasm. This behavior has never before been described in a sporadic form of MTC.

Unlabelled: The high sensitivity of pentagastrin stimulation in detecting primary or metastatic medullary thyroid cancer (MTC) suggests widespread expression of the corresponding receptor type on human MTC. Indeed, autoradiographic studies have demonstrated cholecystokinin (CCK)-B/gastrin receptors not only in more than 90% of MTCs but also in a high percentage of small cell lung cancers, some ovarian cancers, astrocytomas and potentially a variety of adenocarcinomas. The aim of this study was to systematically screen and optimize, in a preclinical model and a pilot clinical study, suitable radioligands for targeting CCK-B receptors in vivo., Methods: A variety of CCK/gastrin-related peptides, all bearing the C-terminal CCK receptor-binding tetrapeptide sequence Trp-Met-Asp-PheNH2 or derivatives thereof, were studied. They were radioiodinated by the lodogen or Bolton-Hunter procedures. The peptides were members of the gastrin or CCK families, which differ by the intramolecular position of a tyrosyl moiety. Their stability and affinity were studied in vitro and in vivo; their biodistribution and therapeutic efficacy were tested in nude mice bearing subcutaneous human MTC xenografts. Diethylenetriamine pentaacetic acid (DTPA) derivatives of suitable peptides were synthesized successfully, and their preclinical and initial clinical evaluations were performed, labeled with 111In., Results: All members of the CCK or gastrin families were stable in serum (with half-lives of several hours at 37 degrees C); nevertheless, the stability of those peptides bearing N-terminal pGlu residues or D-amino acids was significantly higher. In accordance with their comparably low affinity, nonsulfated members of the CCK family showed fairly low uptake in the tumor and other CCK-B receptor-expressing tissues. Sulfated CCK derivatives performed significantly better but also displayed a comparably high uptake in normal CCK-A receptor-expressing tissues. This effect was probably due to their similar affinity for both CCK-A and CCK-B receptors. Best tumor uptake and tumor-to-nontumor ratios were obtained with members of the gastrin family because of their selectivity and affinity for the CCK-B receptor subtype. Pilot therapy experiments in MTC-bearing animals showed significant antitumor efficacy compared with untreated controls. DTPA derivatives of minigastrin were successfully developed. In a pilot clinical study, radioiodinated and 111In-labeled derivatives showed excellent targeting of physiological CCK-B receptor-expressing organs, as well as all known tumor sites., Conclusion: CCK/gastrin analogs may be a useful new class of receptor-binding peptides for diagnosis and therapy of CCK-B receptor-expressing tumors, such as MTC or small cell lung cancer. Nonsulfated gastrin derivatives may be preferable because of their CCK-B receptor selectivity, hence lower accretion in normal CCK-A receptor-expressing organs.

The pretargeting technique referred to as the Affinity Enhancement System (AES) uses bispecific antibodies and radiolabeled bivalent haptens that bind cooperatively to target cells in vivo. Experimental and clinical data demonstrate that AES can deliver large radiation doses to tumor cells with high tumor to normal tissue contrast ratios and long activity residence time in tumors. Preliminary clinical results of radioimmunotherapy of medullary thyroid carcinomas and lung cancers look promising.

Unlabelled: Dual-head coincidence gamma camera 18F-fluorodeoxyglucose (FDG) imaging was compared with FDG PET in the detection of breast cancer and axillary lymph node metastasis., Methods: Both coincidence gamma camera FDG imaging and FDG PET were performed in a cylindrical phantom containing spheres of different sizes and activity ratios (5:1, 10:1 and 15:1) and in 30 women (age range 32-78 y) with suspected breast cancer. Biopsies or mastectomies were performed in all patients. Images were visually assessed, and the count ratio between tumor and normal tissue (T/N ratio) was calculated., Results: In the phantom studies, coincidence gamma camera imaging visualized the smallest sphere (1.0 cm) at a ratio of 15:1 but not at ratios of 5:1 and 10:1. Coincidence gamma camera imaging visualized the other spheres (> or =1.3 cm) at all ratios. PET visualized all spheres at all ratios. In the clinical studies, 22 of 26 breast carcinomas detected by PET were also detected by coincidence gamma camera imaging.. Coincidence gamma camera imaging detected all of the carcinomas > or =2 cm in diameter (n = 10) and 12 of 16 carcinomas <2 cm. In breast carcinomas detected by both PET and coincidence gamma camera imaging, the T/N ratio in non-attenuation-corrected PET (7.12 +/- 7.13) was significantly higher than in coincidence gamma camera imaging (2.90 +/- 1.47, P < 0.005). Four of 8 axillary lymph node metastases detected by PET were detected by coincidence gamma camera imaging. Of 9 axillary lymph node metastases <1.0 cm in diameter, 7 and 3 were detected by PET and coincidence gamma camera imaging, respectively., Conclusion: Coincidence gamma camera imaging is useful in detecting breast carcinoma > or =2 cm in diameter but is not reliable for breast carcinoma <2 cm in diameter. Coincidence gamma camera imaging may be useless or even dangerous in the detection of axillary lymph node metastasis.

Many aspects of thyroid nodule evaluation and management remain controversial. Widespread application of ultrasonography has resulted in frequent discovery of incidental nodules in the general population which has created a management dilemma for physicians. In this paper we have introduced a novel approach for evaluation of solid nodules, using an index derived from ultrasonographic and cytologic studies. Briefly thyroid nodules were classified ultrasonographically into four grades, with increasing score numbers (1-4) as progression to malignantly suspicious lesions was present. Similarly, four grades of a cytologic classification of fine needle biopsy aspirates were introduced with scores of 1-6 (benign to malignant diagnosis). The sum of the ultrasonographic and cytologic scores were the basis of a diagnostic index: benign (2-4), doubtful (5), suspicious (6) and malignant (7-10). Sixty patients with an index equal or higher than 6 were submitted to thyroidectomy and the prevalence of thyroid cancer (n = 46) in the excised nodules was 76.6%. Most series report a 10% to 30% incidence of malignancy in excised nodules with suspicious diagnosis. We concluded that using an index derived from combined ultrasonographic and cytologic studies will result in a better patient selection for surgery.

The authors report a case of medullary carcinoma of the thyroid diagnosed at the 2nd Surgery Clinic of IRCCS Policlinico "San Matteo" in Pavia in a series of 600 cases of thyroid pathology. Having emphasised the rarity of this pathology, the authors report the characteristic pathological aspects. They also outline the clinical signs leading to suspected diagnosis, illustrate the diagnostic techniques used to achieve an early diagnosis and underline the importance of the tumour markers CT and CEA. They identify radical surgery, total thyroidectomy with MND lymphadenectomy, as the therapy of choice, followed by accurate and careful monitoring with a view to ensuring an early diagnosis of renewed disease or recidivation.

Medullary carcinoma of the thyroid (MCT) is malignancy derived from the parafollicular cells (or C-cells) of the thyroid. It is usually sporadic, although it is familial in some cases. Several scintigraphic procedures can provide information regarding the primary and metastatic foci of the tumour. We performed whole-body scanning to establish the pathology of MCT using 201Tl, 99Tcm(V)DMSA and 99Tcm-MIBI in 14 patients, and found average sensitivities of 73%, 82% and 81%, respectively. Moreover, we also scanned three patients with 99Tcm-tetrofosmin and identified two of four pathological foci as well as residual thyroid tissue. The sensitivities of 201Tl, 99Tcm(V)DMSA and 99Tcm-MIBI were 100%, 100% and 85% in identifying lymphadenopathies; 40%, 50% and 71% for soft tissue foci; 100% and 100% for foci in pulmonary parenchyma; and 100%, 66% and 100% for recurrences in thyroid gland. Although 99Tcm(V)DMSA identified all bony metastases in three patients (100%), 99Tcm-MIBI detected only two of three foci (66%) and 201Tl none. 201Tl, 99Tcm-MIBI and 99Tcm-tetrofosmin accumulated in residual thyroid tissue, but 99Tcm(V)DMSA did not, as expected. We conclude that these agents were complementary, since they had different sensitivities in different tissues. The tumour-seeking properties of tetrofosmin are to be evaluated in a larger series.

The thyroid pathology in the paediatric population represents 5% of the total and 1.2% only thyroid pathology correspond to the infantile solitary thyroid nodules. Most of them are asymptomatic and as only sign an increase of volume is observed in the neck. Always we have to ask about the family history because the possibility of medullary carcinoma related with multiple endocrine neoplasias should be investigated (a patient of our series). The thyroid tumor represents 0.5% of all the tumors and of these 10% is in younger than 21 years old. We present 13 patients with thyroid pathology that have required surgical treatment, since 1983 to 1997. Five papillary carcinomas (ages: 7 to 14 years old) that started with a cervical nodule, normal thyroid function and a case of medullary carcinoma, in a multiple endocrine neoplasia (MEN II 2A). In the 5 cases of carcinoma papillary we were carried out total thyroidectomy and later on, postoperative ablative dose of 131I was administered. In the case of the girl with medullary carcinoma was carried out a total tumorectomy and lymph node excision. Finally, seven patients with nodule thyroid were thyroid benign tumors (benign 6 adenomas and 1 cyst colloid, ages: 8 to 15 years old). In all of them we were carried out total surgical excision of the thyroid nodules. Our protocol of study of nodule thyroid includes: 1) thyroid gammagraphy to know the intensity of reception of the isotope; 2) cervical ultrasound; and 3) biopsy or cytopathology of fine needle aspiration of the thyroid gland in children that it dissuades to base the surgical strategy on this test.

Three patients are described who had regional and distant metastases of medullary thyroid cancer detected by somatostatin receptor scintigraphy but not by CT; two had minimal disease that was amenable to surgery. The first patient had been followed for 2 years before having a repeated scan and positive CT, with subsequent surgical removal of metastatic paratracheal nodes. The plasma calcitonin level, however, did not approach normal values after surgery, and a third scan showed persistence of focal uptake in the left paratracheal area of the lower neck, whereas CT was negative. At repeated exploration, a tumor mass of medullary carcinoma, embedded in lymphatic tissue, was removed. Nine months after the last surgical procedure, calcitonin and carcinoembryonic antigen levels were normal. The second patient underwent microdissection of the mediastinum and removal of two metastatic nodes that were demonstrable only by the scintigraphic technique. The plasma calcitonin level subsequently became normal. The third patient, with multiple endocrine neoplasia IIB and associated pheochromocytoma, had bony metastatic involvement of the left shoulder, demonstrable initially on somatostatin receptor scintigraphy and subsequently with radioiodinated metaiodobenzylguanidine but not on CT.

Objective: To analyze the effectiveness of fine needle aspiration (FNA) cytology in a multidisciplinary setting in rural Australia and to compare the imaging (mammographic and ultrasound) appearances and cytomorphologic findings with the final outcome., Study Design: Prospective analysis of ultrasound-guided FNA cytology results from 426 women, aged 40-86 years, with screening-detected mammographic abnormalities. Cases of microcalcification, assessed mainly by stereotactatic core biopsy, were not included in the study. The FNAs were performed at a rural breast screening and assessment program in New South Wales, Australia, over a three-year period between May 1993 and May 1996., Results: Imaging, FNA and combined imaging and FNA results from 426 women were as follows. The imaging diagnoses included 176 (41%) benign, 34 (8%) probably benign, 17 (4%) equivocal, 104 (24%) suspicious and 95 (23%) malignant cases. The FNA findings showed 59 (14%) no epithelial cells seen (nondiagnostic), 175 (41%) benign, 36 (8%) atypical, 41 (10%) suspicious and 115 (27%) malignant. Combined imaging and cytologic results comprised 224 (52.6%) benign, 10 (2.3%) atypical/equivocal, 59 (13.9%) suspicious and 133 (31.2%) malignant cases. All the malignant cases, by combined assessment, had malignant histology, and all the benign cases behaved in a benign fashion. In 80% of the suspicious lesions, the histologic diagnosis was malignant, but only 10% of the atypical/equivocal lesions had malignant histology. The positive predictive value of diagnosis of malignancy by combined imaging and FNA was 100%, and the false negative rate was 0%., Conclusion: Despite the recent surge in the popularity of core biopsy, FNA cytology of impalpable, mammographically detected lesions, when practiced in a multidisciplinary setting, is an extremely accurate test with high sensitivity, specificity, predictive values and efficacy. FNA cytology of the breast is a well-tolerated, relatively noninvasive test with a very low risk of complications. The sensitivity and positive predictive values for malignant and suspicious mammographic categories are also very high.

With the variety of radiopharmaceutical agents and refined imaging techniques, thyroid and parathyroid imaging provides much valuable clinical information. The use of imaging is most important in the follow-up of differentiated (DTC) and medullary thyroid cancer (MTC). Patients with DTC are followed with serum thyroidglobulin and 131I whole body scintigraphy when the serum thyroglobulin level is elevated. When the 131I scintigram is negative, 201Tl scintigraphy may best identify the site of recurrent DTC. Alternative radioisotopes, ultrasound, CT, and FDG PET are also useful in localizing the site of DTC metastases. MTC recurrences and metastases are more difficult to image. Selective venous catheterization is the most sensitive and specific method for detecting areas of recurrent MTC. High-resolution ultrasound, CT, MR imaging, and scintigraphy are all capable of, and useful in, detecting macroscopic foci of metastatic tumor. Somatostatin receptor scintigraphy and 99mTc DMSA have been the most frequently used nuclear imaging agents in patients with recurrent MTC. Imaging for hyperparathyroidism remains controversial. Sestambi has become the preferred isotope for parathyroid scintigraphy; whereas high-resolution ultrasound is also frequently used. Preoperative imaging is being used as a method to allow a unilateral neck exploration, more recently, in conjunction with intraoperative 1-84 PTH assay and with intraoperative use of the gamma probe. Most often, parathyroid imaging is performed before reoperation for persistent hyperparathyroidism.

Unlabelled: The aim of this article was to study the physiopathology of tumoral uptake of 111In-pentetreotide using factorial analysis of dynamic series (FADS) and to assess the usefulness of this analysis in somatostatin receptor scintigraphy., Methods: Forty-one patients were included, 24 women and 17 men. After intravenous injection of 111 MBq 111In-pentetreotide, dynamic image acquisition (68 images of 30 s) began in front of the suspected tumoral site: thoracic in 10 patients with medullary carcinoma of the thyroid and 2 patients with bronchogenic carcinoid, and abdominal in 12 cases of midgut carcinoid and 17 cases of other gastroenteropancreatic neuroendocrine tumors. FADS was performed with FAMIS software. Static images were obtained 4 h and 24 h later. For every patient, surgery and/or clinical follow-up (4 y) was used to classify results as true (T) or false (F) positive (P) or negative (N) and to evaluate both the sensitivity of static images and the usefulness of FADS., Results: Of the 14 cases of carcinoid tumor, 5 patients were TN; 9 patients were TP with static images but only 8 were TP with FADS (a bronchogenic carcinoid of 6 mm was missed). Of the 17 cases of gastroenteropancreatic neuroendocrine tumor, static images were TP in 9 patients, and FADS were TP in 5 of these patients (and 4 FN). Static images and FADS were FN in 4 patients and TN in 3 patients, and in the 2 last patients static images were FP, but FADS were TN. Of the 10 cases of medullary carcinoma of the thyroid, static images and FADS were TN in 1 patient, static images were TP in 3 patients and FADS were TP in 2 of these patients (and 1 FN). In the six last cases, static images were FN, but FADS were FN in 3 patients and TP in 3 patients, showing an infiltrate., Conclusion: FADS demonstrates that tumoral kinetics are similar to those of the spleen. FADS can show a diffuse tumoral uptake corresponding to tumoral infiltrate in medullary carcinoma of the thyroid or in hepatic miliaria, whereas static images were normal or doubtful.

A 54-year-old man with medullary thyroid carcinoma in the thyroid gland was unable to undergo total thyroidectomy because the tumor had invaded the mediastinum. Radiation therapy and chemotherapy were given. Seven years later, intractable diarrhea and abdominal pain appeared, and computed tomography demonstrated hypervascular tumors in the thyroid gland and in the liver. The tumors were successfully treated with percutaneous ethanol injection to a lesion in the thyroid gland and transcatheter arterial embolization followed by percutaneous ethanol injection to tumors in the liver. Transcatheter arterial embolization and percutaneous ethanol injection may be valuable in treating medullary thyroid carcinoma.

Medullary carcinoma of the thyroid (MCT) is an uncommon malignant neoplasm, which occurs sporadically and in three familial syndromes with a dominant autosomal transmission mode. We studied a family of 13 members in which four of them (two males and two females: sons, mother and niece) were involved with MCT. All of them underwent mode-B echography and colour-Doppler echography and pulsed colour Doppler, with measurement of carcinoembryonic antigen (CEA) and calcitonin, in an attempt to delineate a pattern useful to differentiate malignant from benign thyroid pathology. Colour Doppler signal was of little usefulness for histologic characterization in function of vascularization, although it was useful for delineating nodules in non-homogeneous glands.

Unlabelled: The early detection of all tumor sites in patients with medullary thyroid carcinoma (MTC) before primary surgery is important, because MTC tends to metastasize to regional lymph nodes of the neck and mediastinum early during the course of the disease., Methods: In an approach to localize the primary tumor sites and to detect additional tumor involvement, we have performed in 22 patients with MTC either 99mTc(V)-dimercaptosuccinic acid (DMSA) and/or 111In-diethylenetriamine pentaacetic acid-D-Phe-1-octreotide scintigraphy., Results: Indium-111-octreotide (150-200 MBq) identified the primary tumor in 10 of 14 patients (71%), whereas the primary tumor was visualized by 99mTc-DMSA (300-370 MBq) in 10 of 17 patients (58%). In 8 of 22 patients (36%), lymph node metastases were present at the time of diagnosis, as confirmed by histopathology and histochemistry after surgery (all <2 mm). Preoperatively, neither scan was able to detect lymph node involvement in these patients (0/8)., Conclusion: Both 99mTc-DMSA and 111In-octreotide studies have similar sensitivity to localize primary MTC; however, these scans are not able to detect small lymph node involvement (micrometastases) before initial surgery. Unfortunately, both scans have no clinical implication for preoperative staging in patients with MTC.

Detection of recurrence of medullary thyroid carcinoma (MTC) remains a diagnostic problem. Increased serum tumour marker levels frequently indicate recurrence while conventional imaging techniques (CIT) are non-diagnostic. In this study, we performed indium-111 octreotide scintigraphy and CIT in a series of 20 patients with MTC presenting with elevated serum tumour markers after surgery. 111In-octreotide whole-body studies detected 15 pathological uptake foci in 11 of the 20 patients studied and CIT detected 17 lesions in 11 of the 20 patients. Ten patients underwent reoperation, five of them with positive 111In-octreotide scintigraphy and CIT and two with positive isotopic exploration and negative CIT. Surgical findings demonstrated that the results of isotopic study and CIT had been false-positive for MTC in one case (sarcoidosis). The six patients with true-positive 111In-octreotide studies had significantly higher basal calcitonin (CT) and carcinoembryonic antigen (CEA) levels than the patients with negative isotopic studies. The expression of somatostatin receptor (SSTR) subtypes by PC-PCR could be investigated in four cases with a positive isotopic study. Among the three cases with a true-positive study, SSTR2, the SSTR subtype that preferentially binds to the somatostatin analogue octreotide, was detected in two, SSTR5 was demonstrated in the three, and SSTR3 was detected in one. No subtype of SSTR was detected in the case with a final diagnosis of sarcoidosis. We conclude that 111In-octreotide has limited sensitivity in detecting recurrence in patients with MTC, although its sensitivity may improve with high serum CT levels. This radionuclide imaging technique should be employed when conventional imaging techniques are negative or inconclusive or when the presence of somatostatin receptors may provide the basis for treatment with somatostatin analogues.

Unlabelled: The purpose of this study was to evaluate biodistributions and absorbed doses of anti-carcinoembryonic antigen (CEA)/anti-diethylenetriamine pentaacetic acid (DTPA)-indium (anti-DTPA-In) bispecific monoclonal antibody (BsMAb) F6-734 and 125I-labeled DTPA-indium dimer hapten (125I-di-DTPA-In hapten) in athymic mice xenografted with human medullary thyroid cancer., Methods: Bispecific monoclonal antibodies F6-679 (anti-CEA/antihistamine) and G7A5-734 (antimelanoma/anti-di-DTPA-In) were used as irrelevant BsMAbs. Athymic mice inoculated with TT medullary thyroid cancer cells expressing CEA were administered BsMAbs F6-734, F6-679 or G7A5-734 and then, 48 hr later, 125I-di-DTPA-In hapten. Iodine-125-labeled F6 F(ab')2 fragment was injected into other groups of mice. Biodistributions were examined at 30 min and 5, 24, 48 and 96 hr after injection of 125I-di-DTPA-In hapten or 125I-labeled F6 F(ab')2., Results: In mice injected with BsMAb F6-734 and 125I-di-DTPA-In hapten, tumor uptake was 9.1%+/-2.1%, 8.7%+/-3.5%, 8.0%+/-2.3%, 5.1%+/-0.9% and 3.5%+/-1.5% of the injected dose/g at 30 min and 5, 24, 48 and 96 hr, and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios were 37.0+/-12.5, 32.3+/-10.9 and 10.4+/-2.7 at 24 hr. Iodine-125-F6 F(ab')2 fragment showed a tumor uptake of 7.39% injected dose/g and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios of 1.8+/-0.6, 7.3+/-2.9 and 3.6+/-1.6 at 24 hr. In mice injected with F6-679 or G7A5-734, tumor uptake and tumor-to-normal tissue ratios were much lower than in the mice injected with F6-734. These results were confirmed by autoradiographic studies that demonstrated clear tumor-to-normal tissue contrast., Conclusion: This two-step targeting method seems very potent for the diagnosis and therapy of human medullary thyroid cancer and other CEA-producing tumors because it combines high tumor uptake and low normal tissue background.

Early diagnosis of metastases of medullary thyroid carcinoma (MTC) provides the optimal condition for curative outcome. The aim of this study was to appraise the detection of metastases in patients with recurrent MTC using [111In-DTPA-d-Phe1]-pentetreotide and pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] in comparison with histopathological findings. Eighteen MTC patients with persistently elevated tumour marker (calcitonin, carcinoembryonic antigen) levels underwent somatostatin receptor scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide (222 MBq) with early (4 h after injection) and delayed (24 h) whole-body scans and single-photon emission tomography (SPET) imaging. Metabolic whole-body and SPET imaging using 500 MBq 99mTc(V)-DMSA was performed 4 h after injection. Metabolic and receptor imaging revealed 51 sites of focal accumulation in the 18 patients investigated. Comparison with histological findings revealed that metabolic and receptor imaging had a sensitivity of 84% for the diagnosis of MTC. Using [111In-DTPA-d-Phe1]-pentetreotide, SPET discovered four lymph node metastases in two patients in whom planar views had previously identified only one lymph node metastasis, and provided no new information in the other 16 patients. In comparison, SPET studies [using 99mTc(V)-DMSA] additionally localized eight lymph node metastases in four patients and confirmed the diagnosis of hepatic metastases (n=5) in another patient in whom conventional imaging modalities and planar views had previously detected only three liver metastases. Overall, lesion detection sensitivities for 99mTc(V)-DMSA and [111In-DTPA-D-Phe1]-pentetreotide were 69% and 29%, respectively. Five surgically removed foci were adjudged false-positive with respect to MTC metastases. False-positve results were caused by lymphadenitis, an enchondroma and a pheochromocytoma (histologically proven). The smallest lesion identified by metabolic imaging was a 6 mm in diameter lymph node metastasis located in the upper mediastinum. Somatostatin receptor scintigraphy only demonstrated tumour sizes more than 1 cm in diameter. These preliminary results suggest that the combination of metabolic [99mTc(V)-DMSA] and receptor ([111In-DTPA-D-Phe1]-pentetreotide) imaging is more sensitive for tumour localization in patients with recurrent MTC than the use of only one radiopharmaceutical. However, neither 99mTc(V)-DMSA nor [111In-DTPA-D-Phe1]-pentetreotide is specific for MTC and false-positive scintigraphic findings have to be considered. Furthermore, somatostatin receptor scintigraphy cannot visualize small tumour sites (<1 cm). Further studies are needed to evaluate the role of combined metabolic and receptor imaging in the management of patients with recurrent MTC.

Unlabelled: Previous studies of the intraoperative use of a handheld gamma probe to localize metastases and primary tumors of colorectal cancer have shown improved assessment of tumor spread and changes in surgical management based on added information gained by radioimmunoguided surgery. We conducted a prospective study to determine whether intraoperative radiodetection is able to reveal microscopic and occult disease of neuroendocrine tumors [medullary thyroid carcinomas (MTCs), gastroenteropancreatic (GEP) tumors]., Methods: After the injection of 180 MBq [111In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe1]pentetreotide and/or 500 MBq 99mTc-dimercaptosuccinic acid (DMSA) (both for double-nuclide scintigraphy), preoperative somatostatin receptor imaging (12 patients with GEP tumors) and double-nuclide scintigraphy (10 patients with relapsing MTCs were performed. The results were combined with the information obtained from conventional imaging modalities (CT and sonography). Intraoperative radiodetection was performed 24 hr after administration of [111In-DTPA-D-Phe1]pentetreotide or 4 hr after the injection of 99mTc-DMSA using a handheld gamma probe., Results: Intraoperative gamma counting localized 70 somatostatin receptor-positive lesions of GEP tumors, whereas preoperative receptor imaging visualized 74%, surgical palpation visualized 44% and radiological imaging modalities localized only 43%. In 10 patients with recurrent MTCs, the surgeon was successful in localizing and removing 30 tumor lesions using the gamma probe. Twenty-seven of 30 lesions demonstrated tumor involvement, whereas 3 lesions were false-positive (lymphadenitis). Double-nuclide scintigraphy revealed 67% (Octreoscan, 7 of 20; 99mTc-DMSA, 13 of 20), surgical palpation revealed 60% and conventional imaging methods (CT, sonography) revealed only 50% of all lesions detected intraoperatively by the handheld gamma probe. The smallest lesion identified by the handheld probe (not palpated by the surgeon) was a lymph node metastasis (5-mm diameter)., Conclusion: The preliminary data show that intraoperative handheld gamma probe detection of microscopic and occult endocrine tumors is feasible and more sensitive than external scintigraphy and conventional imaging.

Several types of neuroendocrine tumor express high numbers of somatostatin receptors (sstr). We have compared the expression of sstr subtypes with the outcome of octreotide scintigraphy in patients with carcinoids and medullary thyroid carcinoma (MTC) in comparison with Hürthle cell tumors. The effect of sstr activation (octreotide treatment) on tumor markers was also studied in patients with disseminated carcinoid tumors. Six patients with carcinoid tumors (four midgut and two foregut), and three patients with thyroid tumors (one MTC, one Hürthle cell carcinoma, and one Hürthle cell adenoma) were studied. Octreotide scintigraphy visualized tumor sites in all nine patients. Macroscopic tumor was verified at these sites at subsequent surgical exploration. Using Northern blotting and subtype-specific riboprobes, sstr could be detected in all tumors examined. All five sstr subtypes were detected in most of the carcinoid tumors. All six carcinoids expressed sstr2. This was in contrast to the findings for the thyroid tumors analyzed, which also expressed several sstr subtypes but in some cases lacked expression of sstr2. This was also the case for normal thyroid tissue. Clinically, octreotide treatment of the patients with midgut carcinoid tumors resulted in palliation of hormonal symptoms accompanied by a significant reduction of urinary 5-HIAA levels (28-71%). These results indicate that carcinoid tumors frequently express all five sstr subtypes. The thyroid tumors also expressed multiple sstr but could lack expression of sstr2. Nevertheless, these tumors were visualized by octreotide scintigraphy, indicating that sstr2 expression is not a prerequisite for tumor imaging.