Medullary Thyroid Carcinoma Lesions Research Articles

Diagnostic value and cost-effectiveness of FNA-CT versus FNAC for medullary thyroid carcinoma.

To evaluate the diagnostic performance and cost-effectiveness of calcitonin assays in fine-needle aspiration washout fluid (FNA-CT) compared to fine-needle aspiration cytology (FNAC) for medullary thyroid carcinoma (MTC). A total of 27,404 patients from three medical centres between January 2020 and May 2022 were screened for serum calcitonin (sCT). Of whom, 223 patients met endpoints and were enroled for analyses. Based on sCT levels, patients were divided into two groups (group 1: 10 pg/ml< sCT ≤100 pg/ml and group 2: sCT > 100 pg/ml). The diagnostic performance and cost-effectiveness of FNA-CT and FNAC were compared. Most patients (N = 25,228; 92.1%) with thyroid nodules had normal sCT levels. In group 1, 24 and 167 nodules were diagnosed as MTC and non-MTC lesions, respectively. FNA-CT showed better performance in diagnosing MTC than FNAC in terms of sensitivity (100.0% vs. 58.3%), negative predictive value (100.0% vs. 94.3%), and overall accuracy (100.0% vs. 94.7%). In group 2, 67 and 7 nodules were diagnosed as MTC and non-MTC lesions, respectively. The diagnostic performance of FNA-CT was superior to FNAC in terms of sensitivity (100.0% vs. 64.2%), negative predictive value (100.0% vs.22.6%), and overall accuracy (100.0% vs. 67.6%). Furthermore, analysis from the decision tree model showed that FNA-CT was a cost-effective tool for diagnosing MTC lesions. FNA-CT can serve as an auxiliary and cost-effective approach for patients with indeterminate sCT levels to detect occult MTC lesions. FNA-CT can be recommended for patients with sCT >100 pg/ml to overcome the high false-negative rate of FNAC.

Head-to-head comparison of FNA cytology vs. calcitonin measurement in FNA washout fluids (FNA-CT) to diagnose medullary thyroid carcinoma. A systematic review and meta-analysis

PurposeThe sensitivity of cytology after fine needle aspiration (FNA-cytology) in detecting medullary thyroid carcinoma (MTC) is low. To overcome this problem, measuring calcitonin (CT) in washout fluid of FNA (FNA-CT) has been largely diffused and showed good performance. However, no evidence-based study exists comparing systematically the sensitivity of FNA-cytology and FNA-CT. This study aimed to systematically review the literature and collect data allowing a head-to-head comparison meta-analysis between FNA-cytology and FNA-CT in detecting MTC lesions.MethodsThe online databases of PubMed/MEDLINE and Scopus were searched until June 2021. Original articles reporting the use of both FNA-cytology and FNA-CT in the same series of histologically proven MTC lesions were included They were extracted general features of each study, number of MTC lesions (nodule and neck lymph nodes), and true positive and false negatives of both FNA-cytology and FNA-CT.ResultsSix studies were included. The sensitivity of FNA-cytology varied from 20% to 86% with a pooled value of 54% (95% CI 35–73%) and significant heterogeneity. The sensitivity of FNA-CT was higher than 95% in almost all studies with a pooled value of 98% (95% CI 96–100%) without heterogeneity. The sensitivity of FNA-CT was significantly higher than that of FNA-cytology.ConclusionsFNA-CT is significantly more sensitive than FNA-cytology in detecting MTC. Accordingly, FNA-CT represents the standard method to use in patients with suspicious MTC lesions, combined with cytology.

Cytology versus calcitonin assay in fine-needle aspiration biopsy wash-out fluid (FNAB-CT) in diagnosis of medullary thyroid microcarcinoma.

Widespread use of sensitive ultrasound examination led to an increasing detection of medullary thyroid microcarcinoma (micro-MTC). This prospective study evaluated the diagnostic accuracy of Fine-needle Aspiration Biopsy Cytology (FNAB-C) and calcitonin assay in Fine-needle Aspiration Biopsy wash-out fluid (FNAB-CT) in thyroid nodules less than 1 cm with elevated serum calcitonin(sCT). 87 thyroid nodules from 60 patients with elevated sCT (>10 pg/ml) were included and 51 were thyroid nodules less than 1cm. FNAB-CT and FNAB-C were performed to distinguish medullary thyroid carcinoma (MTC) lesions before surgery, histopathologic diagnoses served as main reference standards. FNAB-CT had a greater performance over FNAB-C for preoperative diagnosis of MTC (diagnostic accuracy: 98.85 vs 61.90%, sensitivity: 98.55 vs 55.07%, specificity: 100 vs 97.44%), especially for micro-MTC: FNAB-C established a sensitivity and diagnostic accuracy of 48.78 and 58% respectively, while FNAB-CT reached 97.56% sensitivity and 98.04% diagnostic accuracy. FNAB-CT demonstrated high diagnostic accuracy in diagnosing micro-MTC. Patients with microscopic thyroid nodules and elevated sCT level should perform FNAB-CT to exclude the diagnosis of MTC lesions.

Radiofrequency Ablation: A Novel Treatment Option for Neck Recurrence in Medullary Thyroid Carcinoma

Abstract Background: Medullary thyroid carcinoma (MTC) is an aggressive cancer with cervical lymph node metastases typically found at presentation. The recurrence rate after resection is high (~ 50%)(1), and patients often need multiple surgeries. Radiofrequency ablation (RFA) has been used in treatment of recurrent thyroid cancer when surgery is contraindicated or declined by patients in both Asia and Europe (2). We present the first case of an MTC recurrence treated successfully with RFA in North America. Clinical Case: A 43-year-old female with sporadic metastatic MTC, status post total thyroidectomy and multiple neck surgeries, presented with elevated calcitonin level of 630 pg/mL (normal: &amp;lt; 10 pg/mL). Neck ultrasound showed left tracheoesophageal groove mass, measuring 12 mm X 12 mm X 17 mm, consistent with metastatic MTC on cytopathology with calcitonin washout of 16590 pg/mL (normal: &amp;lt; 10 pg/mL). She had no dysphagia, shortness of breath or hoarseness of voice. Computed tomography (CT) scan of chest confirmed presence of mass, in proximity with left recurrent laryngeal nerve. Serial imaging showed rapid enlargement, with concern for impending aerodigestive tract invasion. Surgical intervention had a high risk of vocal cord paralysis due to the lesion’s location. A multidisciplinary tumor board agreed that thermal ablation aimed at shrinking the mass, as a bridge to systemic therapy, would be the best option. RFA was performed as an outpatient with conscious sedation, after informed consent and observing standard aseptic techniques. Under continuous ultrasound guidance, D5W was injected into left tracheoesophageal groove behind the mass and a continuous infusion of D5W at 15 mL/hr was maintained to protect the nerve from thermal injury. Using a trans-isthmic approach, an 18 G monopolar RFA probe with 5 mm active tip was advanced into the malignant mass and ablation was performed with 35 W power until the entire mass was hyperechoic. Vocal response was monitored throughout the procedure and voice remained normal after RFA. A neck ultrasound at her 6 months follow-up showed ablated lesion measuring 7 mm X 11 mm X 10 mm, representing a 68.6% reduction in volume. Repeat CT scan thorax showed disappearance of mass in left neck region. Conclusion: RFA is a minimally invasive and effective treatment for recurrent cervical MTC lesions, and a viable alternative to surgery, as shown in our case. Future studies should focus on long term follow-up and comparison with surgery with regards to safety and efficacy.

Anti-CEA Pretargeted Immuno-PET Shows Higher Sensitivity Than DOPA PET/CT in Detecting Relapsing Metastatic Medullary Thyroid Carcinoma: Post Hoc Analysis of the iPET-MTC Study.

Pretargeting parameters for the use of anti-carcinoembryonic antigen (CEA) bispecific monoclonal antibody TF2 and the 68Ga-labeled IMP288 peptide for immuno-PET have been optimized in a first-in-humans study performed on medullary thyroid carcinoma (MTC) patients (the iPET-MTC study). The aim of this post hoc analysis was to determine the sensitivity of immuno-PET in relapsing MTC patients, in comparison with conventional imaging and 18F-l-dihydroxyphenylalanine (18F-DOPA) PET/CT. Methods: Twenty-five studies were analyzed in 22 patients. All patients underwent immuno-PET 1 and 2 h after 68Ga-IMP288 injection pretargeted by TF2, in addition to neck, thoracic, abdominal, and pelvic CT; bone and liver MRI; and 18F-DOPA PET/CT. The gold standard was histology or confirmation by one other imaging method or by imaging follow-up. Results: In total, 190 lesions were confirmed by the gold standard: 89 in lymph nodes, 14 in lungs, 46 in liver, 37 in bone, and 4 in other sites (subcutaneous tissue, heart, brain, and pancreas). The number of abnormal foci detected by immuno-PET was 210. Among these, 174 (83%) were confirmed as true-positive by the gold standard. Immuno-PET showed a higher overall sensitivity (92%) than 18F-DOPA PET/CT (65%). Regarding metastatic sites, immuno-PET had a higher sensitivity than CT, 18F-DOPA PET/CT, or MRI for lymph nodes (98% vs. 83% for CT and 70% for 18F-DOPA PET/CT), liver (98% vs. 87% for CT, 65% for 18F-DOPA PET/CT, and 89% for MRI), and bone (92% vs. 64% for 18F-DOPA PET/CT and 86% for MRI), whereas sensitivity was lower for lung metastases (29% vs. 100% for CT and 14% for 18F-DOPA PET/CT). Tumor SUVmax at 60 min ranged from 1.2 to 59.0, with intra- and interpatient variability. Conclusion: This post hoc study demonstrates that anti-carcinoembryonic antigen immuno-PET is an effective procedure for detecting metastatic MTC lesions. Immuno-PET showed a higher overall sensitivity than 18F-DOPA PET/CT for disclosing metastases, except for the lung, where CT remains the most effective examination.

Which Is the Optimal Scan Time of 18F-DOPA PET/CT in Patients With Recurrent Medullary Thyroid Carcinoma?: Results From a Dynamic Acquisition Study.

The aim of this retrospective study was to determine, by dynamic acquisition, the optimal scan time of F-DOPA PET/CT in patients with recurrent medullary thyroid carcinoma (MTC). Twenty-one patients with suspected recurrent MTC underwent dynamic F-DOPA PET/CT (lasting 45 minutes) followed by whole-body scan. Three different time intervals of dynamic acquisition were evaluated: ultra-early phase (2-5 minutes), early phase (5-10 minutes), and late phase (40-45 minutes). The number and SUVmax of all detected lesions among the 3 dynamic acquisition phases were compared on qualitative and semiquantitative analyses. Time-activity curves, SUVmax washout rate between ultra-early or early phase and late phase, and signal-to-noise ratio (SNR) between lesion and background activity were also calculated. At dynamic acquisition, 15 of 21 patients were classified as PET-positive and 6 of 21 as PET-negative, with overall 21 detected lesions. Ultra-early and early imaging provided a better lesion visualization than late phase in more than 70% of cases, as also reflected by SNR (mean SNR reduction between 2 and 45 minutes, -45% ± 19%). Time-activity curves showed a rapid tracer accumulation in MTC lesions, with an average maximum uptake at 2 minutes after injection. Mean lesion SUVmax was 2-fold higher in ultra-early frames compared with last frames (mean washout rate, -44% ± 33%). Finally, compared with whole-body imaging in the same field of view, dynamic acquisition identified 1 additional positive patient and 3 additional lesions in 2 patients. Our study, showing a very fast F-DOPA uptake in MTC lesions, suggests the utility to obtain early PET/CT images, already at 2 to 5 minutes after tracer injection, when maximum lesion tracer uptake is reached.

Use of fine-needle aspirate calcitonin to detect medullary thyroid carcinoma: A systematic review.

The measurement of calcitonin in washout fluids of thyroid nodule aspirate (FNA-calcitonin) has been reported as accurate to detect medullary thyroid carcinoma (MTC). The results from these studies have been promising and the most updated version of ATA guidelines quoted for the first time that "FNA findings that are inconclusive or suggestive of MTC should have calcitonin measured in the FNA washout fluid." Here we aimed to systematically review published data on this topic to provide more robust estimates. A comprehensive computer literature search of the medical databases was conducted by searching for the terms "calcitonin" AND "washout." The search was updated until April 2015. Twelve relevant studies, published between 2007 and 2014, were found. Overall, 413 thyroid nodules or neck lymph nodes underwent FNA-calcitonin, 95 were MTC lesions and 93 (97.9%) of these were correctly detected by this measurement regardless of their cytologic report. The present study shows that the above ATA recommendation is well supported. Almost all MTC lesions are correctly detected by FNA-calcitonin and this technique should be used to avoid false negative or inconclusive results from cytology. The routine determination of serum calcitonin in patients undergoing FNA should improve the selection of patients at risk for MTC, guiding the use of FNA-calcitonin in the same FNA sample and providing useful information to the cytopathologist for the morphological assessment and the application of tailored ancillary tests.

Detection rate of FNA cytology in medullary thyroid carcinoma: a meta-analysis.

The early detection of medullary thyroid carcinoma (MTC) can improve patient prognosis, because histological stage and patient age at diagnosis are highly relevant prognostic factors. As a consequence, delay in the diagnosis and/or incomplete surgical treatment should correlate with a poorer prognosis for patients. Few papers have evaluated the specific capability of fine-needle aspiration cytology (FNAC) to detect MTC, and small series have been reported. This study conducts a meta-analysis of published data on the diagnostic performance of FNAC in MTC to provide more robust estimates. A comprehensive computer literature search of the PubMed/MEDLINE, Embase and Scopus databases was conducted by searching for the terms 'medullary thyroid' AND 'cytology', 'FNA', 'FNAB', 'FNAC', 'fine needle' or 'fine-needle'. The search was updated until 21 March 2014, and no language restrictions were used. Fifteen relevant studies and 641 MTC lesions that had undergone FNAC were included. The detection rate (DR) of FNAC in patients with MTC (diagnosed as 'MTC' or 'suspicious for MTC') on a per lesion-based analysis ranged from 12·5% to 88·2%, with a pooled estimate of 56·4% (95% CI: 52·6-60·1%). The included studies were statistically heterogeneous in their estimates of DR (I-square >50%). Egger's regression intercept for DR pooling was 0·03 (95% CI: -3·1 to 3·2, P = 0·9). The study that reported the largest MTC series had a DR of 45%. Data on immunohistochemistry for calcitonin in diagnosing MTC were inconsistent for the meta-analysis. The presented meta-analysis demonstrates that FNAC is able to detect approximately one-half of MTC lesions. These findings suggest that other techniques may be needed in combination with FNAC to diagnose MTC and avoid false negative results.

Reduced tissue inhibitor of metalloproteinase-2 expression is associated with advanced medullary thyroid carcinoma

Matrix metalloproteinases (MMPs) are enzymes for extracellular matrix remodeling that are involved in tumor growth, progression and metastasis. Among them, MMP-9 has been implicated in tumor angiogenesis. Tissue inhibitor of matrix metalloproteinase (TIMP)-2, a member of the family of MMP inhibitors, induces apoptosis and inhibits various stages of angiogenesis. Previous studies analyzing the expression of MMP-9 and TIMP-2 in medullary thyroid carcinoma (MTC) are scarce. The aims of the current study were to evaluate MMP-9 and TIMP-2 expression in MTC samples and correlate the results with clinical parameters. Paraffin-embedded samples from 77 MTC patients were evaluated for expression by immunohistochemistry. The clinical data in medical records were retrospectively reviewed. In total, 77 patients aged 35.6±17.1 years were enrolled. Of these patients, 36 had hereditary disease (46.8%). Immunohistochemical staining for MMP-9 and TIMP-2 was detected in 89.6 and 93.5% of the samples, respectively. The expression of MMP-9 was not found to correlate with clinical parameters, although, a trend toward a correlation between MMP-9 and distant metastasis was observed (P=0.053). By contrast, TIMP-2 staining was found to correlate with age at diagnosis (P=0.026) and negatively correlate with tumor size and tumoral stage (P=0.002 and P=0.001, respectively). Notably, the highest levels of TIMP-2 expression were observed in patients with intrathyroidal disease. The MMP-9 enzyme involved in extracellular matrix remodeling is overexpressed in MTC lesions and may contribute to tumor vascularization and growth. Reduced levels of TIMP-2 expression may be implicated in tumor progression and spread of disease.

Appearance of follicular thyroid carcinoma and medullary thyroid carcinoma on color ultrasound and pathological examination in 98 patients

Objective To study the appearance of follicular thyroid carcinoma (FTC) and medullary thyroid carcinoma (MTC) on color ultrasound and the value of differential diagnosis of ultrasound.Methods The data on 41 patients with FTC and 51 patients with MTC lesions were analyzed retrospectively.The ultrasound appearance and pathological features of these two types of cancer were compared.Results Follicular carcinoma had a higher incidence rate than medullary carcinoma in female (P＜0.05).Medullary carcinoma was easier to occur lymph node metastasis than follicular carcinoma (P＜0.05).Most of ollicular carcinomas had clear surroundings without interior calcification,while medullary carcinoma had unclear surroundings with internal calcification (P＜0.05).Blood supply to cancerous tissues also differed between the two types of cancer (P＜0.05).Conclusions Color ultrasound appearance is of significance in the differential diagnosis of follicular thyroid carcinoma and medullary thyroid carcinoma,which is helpful in the establishment of therapeutic regimens. Key words: Thyroid carcinoma;  Follicular;  Medullary

New Diagnostic and Therapeutic Tools for Thyroid Cancer

Thyroid cancer is the commonest endocrine malignancy but represents only 1% of all cancers. Although the prognosis of differentiated thyroid cancer is good, the survival time of anaplastic and of medullary thyroid cancer is still very short. More precise diagnosis with better stratification of patients and identification of risk patients may improve the prognosis of thyroid cancer. Treatment of thyroid cancer is multidisciplinary and involves endocrinologists, nuclear medicine specialists, and surgeons. The spectrum of contributions to this special issue in International Journal of Endocrinology is well reflecting this situation. The contributions to this special issue, two reviews and three studies, report mainly on laboratory and imaging techniques to improve diagnosis in thyroid cancer. J. Hannallah et al. emphasize the multimodal approach in diagnosis and managing patients with poorly differentiated thyroid cancer in their review. The identification of poorly differentiated thyroid cancer has been complicated by the lack of clear criteria for diagnosis. A panel of histological, immunohistochemical, and genetic markers and clinical parameters is listed which are typical for this thyroid carcinoma entity. The value of current treatment possibilities is critically discussed. In the paper review by G. Treglia et al. the role of Fluorine-18-Fluorodeoxyglucose positron emission tomography in aggressive subtypes of different thyroid cancer types (Hurthle cell, anaplastic, poorly differentiated, more aggressive histological subtypes of differentiated thyroid cancer, and metastases) is discussed. FDG-PET-positivity in radio-iodine-refractory differentiated thyroid cancer appears to predict more aggressive tumor progression. Data on imaging of medullary thyroid carcinoma lesions using glucagon-like peptide 1 by [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 are presented by D. Pach et al. Radioactively labeled GLP-1 analogues are successfully used in patients with insulinoma but the diagnostic value in medullary thyroid cancer is not clear. According to the first preliminary data, the analogues may possess a confirmatory role in lesions where inconsistent results are obtained with other imaging procedures. S. H. Hsieh et al. in their study identified male gender as prognostic parameter for higher recurrence in papillary thyroid cancer in stages II–IV. The study by B. C. Ahn et al., by contrast, deals with a very established clinical test, the measurement of serum thyroglobulin levels, for the identification of recurrent lesions in differentiated thyroid cancer. The importance of patients' antithyroglobulin levels in the calculation of thyroglobulin levels is addressed. The identification of potentially aggressive subtypes of thyroid cancer and the early detection of recurrent lesions play key roles in the managing of the patient. By compiling these papers, we hope to add some knowledge with respect to screening and postoperative care particularly of the more aggressive thyroid cancer types. Eleonore Frohlich Richard Wahl Barbara Czarnocka Leonidas Duntas

Comparison of 18F-DOPA, 18F-FDG and 68Ga-somatostatin analogue PET/CT in patients with recurrent medullary thyroid carcinoma

To retrospectively evaluate and compare (18)F-FDG, (18)F-DOPA and (68)Ga-somatostatin analogues for PET/CT in patients with residual/recurrent medullary thyroid carcinoma (MTC) suspected on the basis of elevated serum calcitonin levels. Included in the study were 18 patients with recurrent MTC in whom functional imaging with the three tracers was performed. The PET/CT results were compared on a per-patient basis and on a per-lesion-basis. At least one focus of abnormal uptake was observed on PET/CT in 13 patients with (18)F-DOPA (72.2% sensitivity), in 6 patients with (68)Ga-somatostatin analogues (33.3%) and in 3 patients with (18)F-FDG (16.7%) (p < 0.01). There was a statistically significant difference in sensitivity between (18)F-DOPA and (18)F-FDG PET/CT (p < 0.01) and between (18)F-DOPA and (68)Ga-somatostatin analogue PET/CT (p = 0.04). Overall, 72 lesions were identified on PET/CT with the three tracers. (18)F-DOPA PET/CT detected 85% of lesions (61 of 72), (68)Ga-somatostatin analogue PET/CT 20% (14 of 72) and (18)F-FDG PET/CT 28% (20 of 72). There was a statistically significant difference in the number of lymph node, liver and bone lesions detected with the three tracers (p < 0.01). In particular, post-hoc tests showed a significant difference in the number of lymph node, liver and bone lesions detected by (18)F-DOPA PET/CT and (18)F-FDG PET/CT (p < 0.01 for all the analyses) and by (18)F-DOPA PET/CT and (68)Ga-somatostatin analogue PET/CT (p < 0.01 for all the analyses). The PET/CT results led to a change in management of eight patients (44%). (18)F-DOPA PET/CT seems to be the most useful imaging method for detecting recurrent MTC lesions in patients with elevated serum calcitonin levels, performing better than (18)F-FDG and (68)Ga-somatostatin analogue PET/CT. (18)F-FDG may complement (18)F-DOPA in patients with an aggressive tumour.

Increased Expression of Vascular Endothelial Growth Factor and Its Receptors, VEGFR-1 and VEGFR-2, in Medullary Thyroid Carcinoma

Vascular endothelial growth factor (VEGF-A) expression is upregulated in the majority of human tumors, where it stimulates proliferation, migration, and survival of endothelial cells. Studies have suggested that VEGF inhibitors can be used as an alternative therapy in medullary thyroid carcinoma (MTC), but data about expression of VEGF-A and its receptor in this tumor are scarce. The aims of this study were to evaluate VEGF-A, VEGF receptor (VEGFR)-1, VEGFR-2, and microvessel density (MVD) expression in MTC samples and correlate it with clinical parameters. Paraffin-embedded samples from 38 MTC patients were evaluated for VEGF-A, VEGFR-1, VEGFR-2, and MVD expression by immunohistochemistry. Clinical data were retrospectively reviewed in medical records. Thirty-eight patients aged 31.8 +/- 17.1 years were enrolled. Twenty-seven patients had hereditary disease (71.1%). Twenty-five of them were found to have multiple endocrine neoplasia (MEN) 2A and two were found to have MEN 2B. VEGF-A immunohistochemical staining was detected in 95% (36/38), VEGFR-1 in 96% (36/37), and VEGFR-2 in 91% (31/34) of MTC samples. Age at surgery was positively correlated with VEGFR-2 (p = 0.003). There was no correlation between VEGF-A, VEGFR-2, and tumor stage (tumor node metastasis). Nevertheless, VEGFR-1 was found to be inversely correlated with tumor node metastasis (p = 0.034). We also observed a trend toward an association between VEGFR-1 signal intensity and cure of disease, although this did not reach statistical significance (p = 0.054). Neither VEGF-A nor VEGFR-2 was associated with disease outcome after a median follow-up period of 5 years (p = 0.882 and p = 0.236, respectively). As expected, MVD was correlated with age at surgery (p = 0.005) and tumor size (p = 0.03). Patients with the hereditary form of the disease had a stronger intensity for VEGFR-1 (p = 0.039), whereas patients with sporadic disease displayed higher MVD counts (44 [27-63] vs. 21 [9-49], p = 0.018). The VEGF-A, VEGFR-1, and VEGFR-2 immunoreactive proteins are overexpressed in MTC lesions and might be implicated in tumor progression. It is not clear, however, if expression of these molecules provides prognostic information regarding the spread or outcome of MTC.

Clinical Value of 18-Fluorine-Fluorodihydroxyphenylalanine Positron Emission Tomography/Computed Tomography in the Follow-Up of Medullary Thyroid Carcinoma

18-Fluorine-fluorodihydroxyphenylalanine positron emission tomography ((18)F-DOPA PET) is a sensitive method for detecting medullary thyroid carcinoma (MTC). The advent of PET/computed tomography (CT) has enabled more sensitive and specific lesion identification using various tracers in many other tumors. The aim of this study was therefore to test the hypothesis that combined (18)F-DOPA PET/CT more accurately detects MTC lesions than each modality does alone. Twenty-eight consecutive (18)F-DOPA PET, CT, and (18)F-DOPA PET/CT scans of patients followed up for sporadic MTC or multiple endocrine neoplasia 2 syndrome-associated MTC were reviewed retrospectively in randomized sequence by two blinded readers, one a nuclear medicine physician and the other a radiologist, with extensive experience interpreting such images. Of 18 lesions detected concurrently by the three modalities, PET identified all as positive for MTC, but was unable to definitively localize 4 (22%) lesions. CT could definitively localize all 18 lesions, but could not definitively diagnose or exclude MTC in 6 (33%) lesions. Further, CT falsely identified as MTC-negative one lesion that was judged to be MTC-positive by both PET and PET/CT. Only PET/CT scans accurately characterized and localized all 18 lesions. On a per patient basis, the sensitivity of (18)F-DOPA PET/CT for MTC was 74% and the specificity, 100%. In the present series, no truly MTC-positive (18)F-DOPA PET/CT case was found in patients with basal human calcitonin (hCt) levels under 60 pg/mL, and conversely, no truly MTC-negative PET/CT case was found in patients with basal hCt over 120 pg/mL. Between hCt concentrations of 60 and 150 pg/mL true-negative, false-negative, and true-positive scans all were obtained. (18)F-DOPA PET/CT had 100% sensitivity and specificity when hCt at the time of scanning was over 150 pg/mL, the threshold at which the 2009 American Thyroid Association guidelines recommend performing additional imaging including (18)F-DOPA PET/CT. (18)F-DOPA PET/CT allows for a more accurate diagnosis and localization of MTC lesions than do (18)F-DOPA PET or CT alone. Supporting the recent American Thyroid Association recommendations on additional imaging in MTC, (18)F-DOPA PET/CT appears to have 100% sensitivity in patients with hCt over 150 pg/mL.

Ultrasonographic Findings of Medullary Thyroid Carcinoma: a Comparison with Papillary Thyroid Carcinoma

ObjectiveThis study was designed to evaluate the ultrasonographic (US) findings of medullary thyroid carcinoma (MTC) as compared to findings for papillary thyroid carcinoma (PTC).Materials and MethodsThe study included 21 cases of MTC that were surgically diagnosed between 2002 and 2007 and 114 cases of PTC that were diagnosed in 2007. Two radiologists reached a consensus in the evaluation of the US findings. The US findings were classified as recommended by the Thyroid Study Group of the Korean Society of Neuroradiology and Head and Neck Radiology (KSNHNR) and each nodule was identified as suspicious malignant, indeterminate or probably benign. The findings of medullary and papillary carcinomas were compared with use of the chi-squared test.ResultsThe common US findings for MTCs were solid internal content (91%), an ovoid to round shape (57%), marked hypoechogenicity (52%) and calcifications (52%). Among the 21 cases of MTC nodules, 17 (81%) were classified as suspicious malignant nodules. The mean size (longest diameter) of MTC nodules was 19 ± 13.9 mm and the mean size (longest diameter) of PTC nodules was 11 ± 7.4 mm; this difference was statistically significant (p < 0.05). An ovoid to round shape was more prevalent for MTC lesions than for PTC lesions (p < 0.05).ConclusionThe US criteria for suspicious malignant nodules as recommended by the Thyroid Study Group of the KSNHNR correspond to most MTC cases. The US findings for MTC are not greatly different from PTC except for the prevalence of an ovoid to round shape.

Potential Absence of Prognostic Implications of Severe Preoperative Hypercalcitoninemia in Medullary Thyroid Carcinoma

To evaluate preoperative hypercalcitonine-mia further as a marker of prognosis in patients with medullary thyroid carcinoma (MTC). We reviewed the clinical and laboratory data in six patients (four men and two women, 39 to 76 years old)--three with sporadic MTC, one with familial MTC, and two with multiple endocrine neoplasia type 2A--who had preoperative basal serum calcitonin levels of 400 to 16,000 pg/mL (normal, 0 to 19). Pentagastrin stimulation was performed in patients who had preoperative basal calcitonin levels less than 1,000 pg/mL, and responses ranged from 2,600 to 8,500 pg/mL. Thyroidectomy revealed intrathyroidal MTC in four patients; MTC and nodal metastatic lesions were present in two. The tumor cells were immunoreactive with anti-calcitonin immunoperoxidase staining. Serum calcitonin and carcinoembryonic antigen levels were normal postoperatively. In serial postoperative evaluation during a follow-up period of 2 to 9 years, stimulated peak plasma calcitonin levels after pentagastrin or calcium infusion were normal (in five patients) or near normal (in one patient), without clinical evidence of recurrent disease. The two patients with nodal metastatic disease have had normal calcitonin levels during a mean duration of follow-up of approximately 3 years. Pronounced preoperative hypercalci-toninemia does not necessarily preclude a favorable short-term outcome in patients with MTC.

Combined use of 111in-DTPA-D-Phe-1-octreotide (OCT) and 123I-vasoactive intestinal peptide (VIP) in the localization diagnosis of medullary thyroid carcinoma (MTC)

Although serum calcitonin and CEA are sensitive indicators for the presence of medullary thyroid carcinoma (MTC), the localization of tumor sites may be very difficult. In an approach to localize MTC lesions we performed comparative in vivo studies in 12 patients with primary MTC and in 4 patients with suspected recurrent MTC using 123I-VIP (150 MBq/1 μg) and 111In-DTPA-D-Phe-1-octreotide ( 111In-OCT; 150 MBq/1 μg). Despite elevated calcitonin values in all patients with suspected recurrent or metastatic lesions, both ultrasound and computed tomography (CT) were unable to localize a tumor site. 111In-OCT localized the primary tumor in the thyroid gland in 7 of 11 patients (63.5%). In 2 of 4 patients (50%) with suspected recurrent MTC, pathological uptake of 111In-OCT in the mediastinum or liver was demonstrable. In none of the 11 patients did 123I-VIP-receptor scanning indicate primary, recurrent, or metastatic tumor lesions. In vitro binding studies showed an absence of high-affinity VIP receptors in MTC tissue, whereas high-affinity 111In-OCT receptors were present in 4 of 6, and low-affinity 123I-VIP as well as 111In-OCT receptors were present in 6 of 6 MTC tissue samples. We conclude that somatostatin receptor scanning using 111In-OCT may visualize primary MTC, but it has only a low sensitivity in the detection of recurrent disease. The 123I-VIP-receptor scan is not helpful in the localization diagnosis of primary or recurrent MTC.