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Background: Medullary carcinoma of the colon is a rare subtype of colorectal cancer that has a unique, and sometimes varied, clinical and histologic profile. It usually presents in adult patients older than 50 years. Here, we report a unique case of young male patient who initially presented with abdominal pain followed by a large bowel obstruction., Case Presentation: A 40-year-old SriLankan male presented with right-sided abdominal pain and on examination, there was a palpable right iliac fossa mass. Colonoscopy and a computed tomography scan revealed cecal mass. Later, while waiting for elective resection, the patient developed symptoms and signs of a large bowel obstruction. He underwent a laparoscopic right hemicolectomy with an uneventful postoperative course. The histopathologic evaluation of the resected specimens showed invasive carcinoma with syncytial growth pattern, foci of lymphoid host response, and dirty necrosis, in keeping with a medullary carcinoma pT4a pN2b. Unlike most reported medullary carcinoma cases, this patient was young and caudal-related homeobox transcription factor 2 positive., Conclusion: We have reported another case of medullary carcinoma of the colon in a young patient with unique histologic characteristics. Reporting such cases helps in refine understanding of the histologic and genetic, as well as clinical, phenotypes of medullary carcinoma of the colon., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Tumor-to-tumor metastasis is a rare phenomenon in which primary tumor cells metastasize to other tumors. Herein, we report an extremely rare case of tumor-to-tumor metastasis of medullary thyroid carcinoma to a paraganglioma in a patient with multiple endocrine neoplasia type 2B. Based on genetic examination, a 36-year-old woman was diagnosed with multiple endocrine neoplasia type 2B when she was 24 years old. She had a history of total thyroidectomy for medullary thyroid carcinoma and bilateral adrenalectomy for pheochromocytomas, which were performed when she was 15 years and 29 years old, respectively. Follow-up computed tomography demonstrated a retroperitoneal tumor of 30 mm in diameter beside the left kidney and a liver tumor of 16 mm in diameter located in segment 6. The retroperitoneal and liver tumors were surgically resected and examined by a pathologist. Histological examination revealed the classic Zellballen pattern in the retroperitoneal tumor, rendering the diagnosis of a paraganglioma recurrence. Inside the tumor, a white nodule positive for carcinoembryonic antigen, weakly positive for calcitonin, and negative for tyrosine hydroxylase, was identified and diagnosed as a metastatic medullary thyroid carcinoma with high malignant potential. The liver lesion was diagnosed as a metastasis of the medullary thyroid carcinoma. This is the first report of tumor-to-tumor metastasis of medullary thyroid carcinoma to paraganglioma in a patient with multiple endocrine neoplasia type 2B twenty years after total thyroidectomy.

Objective: Recently, several scientific societies designed ultrasound (US) risk stratification systems (RSS) to guide the workup of thyroid nodules and decide which nodules should undergo fine-needle aspiration cytology (FNAC). However, these systems have been developed against papillary thyroid carcinoma, and scanty data on their role in identifying medullary thyroid carcinoma (MTC) are available. The aims of this study are to describe the US features of MTC and evaluate the performance of RSS in identifying MTC., Methods: Data of 152 consecutive patients with MTC was evaluated. The results of the pre-operative neck US of all patients were collected. Ultrasound features of each MTC were evaluated and classified according to the five main RSS available., Results: Median MTC dimension was 1.3 cm. Most of the nodules showed solid composition, hypoechoic pattern, and regular margins. About half of them showed the presence of calcifications, but only a subgroup had microcalcifications. A minority of the nodules showed a 'taller than wide' shape. Only 7.9% of all MTC showed the simultaneous presence of at least four US features suggestive of malignancy. Ultrasonographic high-risk of malignancy of the MTC included in the five RSS, varied from 45.4 to 47.4%, and performing FNAC was suggested in only 48.7 to 63.8% of all MTC., Conclusions: In this series, neither single nor the association of US features are specific for MTC. The five main RSS correctly identify less than 50% of MTC and do not suggest performing FNAC in about half of them with potentially missed or delayed diagnosis.

Introduction: Renal medullary carcinoma (RMC) is a highly lethal adenocarcinoma with a propensity for widespread metastatic disease in young patients. It is strongly associated with sickle cell trait and shows the loss of SMARCB1 (also known as INI1 or BAF47) protein expression. In the present study, we reviewed a series of 12 patients for whom the cytology specimens played a significant role in patient treatment., Materials and Methods: We performed a retrospective case review of patients with a history of RMC from 3 large tertiary care pathology practices., Results: A total of 12 patients were identified with histologically confirmed RMC who had had pleural, pericardial, or urine specimens involved by their disease or had undergone initial kidney fine needle aspiration. Patient age ranged from 13 to 37 years (median, 21.5 years). All 12 patients were black or of African descent, and 10 had a confirmed history of sickle cell trait. Of the 12 patients, 11 (92%) had fluid specimens involved by metastatic tumor at some point in their clinical course, and 4 (33%) had initially presented with pericardial and/or pleural effusions or urine specimens that were positive for malignancy. Cytologic examination predominantly showed fragments of 3-dimensional "tumor balls" with smooth borders, fine pale cytoplasm with vacuolization, and highly pleomorphic nuclei with irregular nuclear membranes and coarse to vesicular chromatin and single prominent nucleoli., Conclusions: The cytomorphology of RMC involving serous fluids is nonspecific and in keeping with metastatic high-grade adenocarcinoma. In a young patient presenting with no history of malignancy and a pleural or pericardial effusion, triaging the material for ancillary studies and a nuanced assessment of patient history and radiologic findings will be critical., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Mucinous and medullary breast cancers (BCs) have different histological substrates that manifest as different imaging features on mammography, ultrasound, and MRI. The aim of the present review is to demonstrate the differences between these two rare BC subtypes and to describe the microscopic features, review the imaging methods for detection of both cancer subtypes, illustrate the imaging findings and present useful pearls and pitfalls. Out of a total of 30 patients with mucinous BC and nine with medullary BC, we have selected typical and also unusual imaging features that best represent these cancers. The patients underwent a mammography and breast ultrasound followed by magnetic resonance imaging. We briefly exhibit histological characteristics for a better understanding of the imaging aspects., (Copyright © 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Renal medullary carcinoma is a rare and highly aggressive tumor seen almost exclusively in young individuals of African descent with sickle cell disease. Here, we describe a case of a 29-year-old man, who did not have sickle cell disease, with pathologically confirmed renal medullary carcinoma using dual-time FDG PET/CT.

Background: To identify the sonographic features that help to differentiate medullary thyroid microcarcinomas (MTMCs) from papillary thyroid microcarcinomas (PTMCs)., Methods: A total of 46 MTMCs in 41 patients and 136 PTMCs in 104 patients that were proven by surgery and pathology were included in the study. Patient age and nodule size were analyzed by independent sample t-tests, and sex, multiplicity and cervical lymph node metastases were analyzed by χ 2 or Fisher's exact tests. Univariate analysis and multivariate logistic regression analysis were performed on the sonographic features of thyroid nodules, including location, shape, boundary, margin, peripheral halo ring, echogenicity, composition, calcifications and vascularization., Results: Compared with the corresponding number of patients with PTMCs, more MTMC patients had cervical lymph node metastases (P = 0.040). There were no significant differences in age, sex, nodule size, multiplicity, location, boundary, margin, peripheral halo ring, echogenicity or microcalcifications between MTMCs and PTMCs (P > 0.05 for all). However, significant differences were found in shape (P = 0.000), composition (P = 0.032), macrocalcifications (P = 0.004) and vascularity (P = 0.000) between the two groups., Conclusions: There were some overlapping sonographic features between MTMCs and PTMCs. However, MTMCs tended to have a > 50% solid composition, be ovoid to round nodules with macrocalcifications and be hypervascular. Cervical lymph node metastases were more common in MTMC patients.

Background: Hereditary medullary thyroid carcinoma (MTC) is mainly caused by germline mutations in the RET proto-oncogene, which accounts for 20-30% of all MTC according to foreign studies. However, no English literatures have reported Chinese hereditary MTC. Here, we reported two Chinese brothers with MTC that caused by germline RET mutation., Case Presentation: The younger brother was diagnosed with MTC at 29 years ago and suffered recurrence more than 10 years. For elder brother, the diagnosis of MTC was made by postoperative pathological examination at age 61. Both patients received total thyroidectomy and lymph node dissection. Since they had a significant family history for MTC, genetic detection was performed and identified a germline mutation in RET exon 10 (p.C620Y). This mutation was also detected in their offspring, indicating a moderate risk of MTC., Conclusions: This is the first report presenting a Chinese family with hereditary MTC caused by the RET p.C620Y variant. This case series emphasize the importance of genetic detection of RET proto-oncogene for MTC patients, and bring out managements for individuals after detection of RET mutations.

Background: The primary aim of this study was to evaluate the therapeutic efficacy and outcome of 177 Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in somatostatin receptor-positive metastatic medullary thyroid carcinoma (MTC), including progression-free survival (PFS) and overall survival (OS), and also to determine the various prognostic variables. The secondary aim was toxicity assessment of PRRT in this group of patients., Methods: A total of 43 somatostatin receptor-positive metastatic MTC patients, treated with 177 Lu-DOTATATE PRRT in a large tertiary care center, were included in this analysis. After receiving the therapy, post-treatment response evaluation was undertaken for symptomatic and biochemical responses (serum calcitonin) and imaging responses with 68 Ga-DOTATATE, 18 F-FDG PET-CT, CeCT (PERCIST and RECIST 1.1 criteria). Calcitonin doubling time (CtnDT) was calculated by the American Thyroid Association calculator. The adverse events were graded according to the NCI-CTCAE v5.0 criteria. The observed Kaplan-Meier curves for both PFS and OS since first PRRT were compared with CtnDT (more than 24 months vs less than 24 months) by log-rank (Mantel-Cox) test. The prognostic variables were investigated for their association with CtnDT and response to PRRT using Cox proportional-hazards model., Results: The median OS was 26 months (95% CI 16.6-35.3 months) and the median PFS 24 months (95%.CI: 15.1-32.9 months). Following 177Lu-DOTATATE PRRT, the observed median PFS and OS was longer in patients who had CtnDT more than 24 months compared to those with CtnDT less than 24 months (median PFS not yet reached vs 10 months and median OS 60 months vs 20 months). Assessing from the time-point of first 177 Lu-DOTATATE PRRT cycle, the patients with CtnDT more than 24 months had a significantly longer PFS (P < .001) and OS (P < .001) compared to those with less than 24 months. Less than 5 lesions, FDG uptake in lesions (SUVmax of <5) and patients alive at the time of analysis were the significant variables for association with CtnDT (more than 24 months). Out of 43 patients, 26 were responders (61%) and 17 nonresponders (39%) based upon PERCIST criteria, and 27 were responders (62%) while 16 patients were nonresponders (38%) based upon RECIST 1.1 criteria. The univariate analysis showed significant association between responses to PRRT with following prognostic variables: (a) size of lesions (<2 cm) and (b) FDG uptake in lesions (SUVmax of <5). PRRT was well tolerated in all patients without any major grade 3 or 4 toxicity., Conclusion: The results demonstrated that, 177 Lu-DOTATATE is a potentially efficacious and safe therapeutic option in SSTR avid metastatic MTC patients., (© 2019 Wiley Periodicals, Inc.)

Purpose: Minimally invasive image-guided thermal ablation has been proposed as alternative to surgery for treatment of benign thyroid nodules and recurrent differentiated thyroid carcinoma. Here, we report for the first time the use of radiofrequency ablation (RFA) in a patient with non-metastatic medullary thyroid carcinoma (MTC) who did not undergo surgery due to high anesthesiological risk., Methods and Results: A 64-year-old woman was referred to our institution for a routine endocrinological visit. No thyroid-related symptoms were present. She had a history of metabolic, cardiovascular and neurological diseases. On clinical examination, a nodular lesion of about 10 mm was palpable in the right thyroid lobe; ultrasonography (US) confirmed the presence of a 13 mm thyroid nodule in the lower pole of the right lobe, that was hypoechoic and with regular margins. Serum calcitonin (Ctn) level was significantly high (647 pg/mL). Fine-needle aspiration (FNA) of the thyroid nodule was negative for malignant cells, but the marked increase of Ctn level in the FNA wash-out fluid confirmed the diagnostic suspicion of MTC. Since patient refused surgery due to high anesthesiological risk, percutaneous US-guided RFA in single session was performed. At 6-months follow-up the serum Ctn level decreased from the initial value of 647 pg/mL, reaching near-normal range (15 pg/mL), and neck ultrasound showed a complete necrosis of the tumour. Afterward, serum Ctn slowly increased to 49 pg/mL at 15-month follow-up. The US performed at 6 and 12 months of follow-up revealed fibrotic tissue in place of the thyroid nodule, without evidence of cervical lymph-node metastases., Conclusions: This clinical case suggests that RFA may be effective and safe for treatment of MTC when surgery cannot be performed.

Objective: Metastatic disease is common in medullary thyroid carcinoma (MTC) and it is usually detected by raising calcitonin and carcinoembryonic antigen (CEA) levels. Nuclear medicine imaging has an important role in lesion identification/characterisation. We aim to compare 68 Ga-DOTANOC PET/CT and 18 F-FDG PET/CT performance and to explore the correlations between tumoral markers and functional imaging., Methods: This a retrospective cross-sectional study including 13 patients with MTC and high calcitonin/CEA levels that underwent both 68 Ga-DOTANOC PET/CT and 18 F-FDG PET/CT., Results: 68 Ga-DOTANOC PET/CT identified MTC metastases in 2twopatients that were 18 F-FDG-negative (sensitivity of 69.2% vs. 53.9%, respectively). 68 Ga-DOTANOC PET/CT also detected a higher number of lesions than 18 F-FDG PET/CT in seven patients, with only one patient showing the opposite pattern. Both differences lacked statistical significance (p = 0.50 and p = 0.86, respectively) but 68 Ga-DOTANOC PET/CT better performance allowed changes in patients' management. 68 Ga-positive/ 18 F-FDG-negative patients were the ones with the lowest calcitonin doubling time and presented a CEA doubling time >24 months, while the patient with more 18 F-FDG-positive lesions was the one with the highest CEA/calcitonin ratio. The number of lesions found in 68 Ga-DOTANOC PET/CT were correlated with calcitonin levels (r = 0.73; p < 0.01) but not with CEA ones (r = 0.42; p = 0.15). The number of 18 F-FDG hypermetabolic focus were correlated with CEA levels (r = 0.60; p < 0.05) but not with calcitonin (r = 0.48; p = 0.09)., Conclusions: This is the first study to describe a positive correlation between 68 Ga-positive lesions and calcitonin levels and between 18 F-FDG-positivity and CEA levels. Tumoral markers pattern in metastatic MTC could help clinicians to decide which exam to perform first.

Purpose: Surgical removal is recommended for recurrent thyroid carcinomas (RTCs) unable to uptake radioiodine and/or not responsive to chemotherapy. However, repeated neck dissection is difficult for surgeons. Thus, radiofrequency ablation (RFA) was proposed for RTCs. The aim of this prospective study is to assess RTC treatment response after RFA, according to well-established criteria., Methods: Sixteen lesions in 13 patients were treated by RFA. All patients refused/were excluded from repeated surgery or other conventional therapy. CT and US examinations were performed before RFA to evaluate lesion volume and vascularization. All RFA procedures were performed under US-guidance by an 18-gauge, electrode. Treatment response was evaluated by CT, according to RECIST 1.1 and to mRECIST guidelines; CT examinations were performed during follow-up (6-18 months); the volume of residual vital tumour tissue and the percentage of necrotic tissue were estimated by contrast enhanced CT., Results: RFA was well tolerated by all patients; in two cases laryngeal nerve paralysis was observed. Mean pre-treatment volume was 4.18 ± 3.53 ml. Vital tumour tissue and percentage of necrosis at 6, 12 and 18 months were 0.18 ± 0.25, 0.11 ± 0.13, 0.29 ± 0.40 ml and 91.9 ± 11.1, 90.4 ± 13.3, 80.8 ± 23.1%. According to RECIST 1.1, target lesion response was classified as complete response (CR) in one case, partial response (PR) in 11/16, stable disease in 4/16 cases. According to mRECIST, 11/16 cases were classified as CR and the remaining 5 as PR., Conclusion: RFA is a safe procedure to treat the viable tumour tissue and to reduce the RTC volume; as to the criteria to assess treatment response, mRECIST appears to be more accurate.

Introduction: Neck dissection is a part of the standard surgical procedure in the management of head and neck malignancy. Diplopia following neck dissection is a rare entity; hence, its diagnosis and management strategies needed to be discussed for prevention of its grave consequences., Case Report: A 30-year-old male patient presented with binocular horizontal diplopia following total thyroidectomy and neck dissection. On evaluation, there was internal jugular vein (IJV) thrombosis followed by cerebral venous sinus thrombosis (CVST). After meticulous medical management with diuretics and antiplatelet drugs, diplopia resolved completely and normal vision was restored., Conclusion: Therapeutic ligation of internal jugular vein during neck dissection may result in IJV thrombosis followed by CVST leading to raised intracranial tension (ICT). It has to be anticipated and addressed as early as possible to prevent its grave consequences like blindness and death.

Introduction: Medullary carcinoma accounts for 1-2% of all thyroid malignancies. 13-20% of patients present with distant metastasis, with 45% of the cases affecting the liver., Clinical Case: A 50-year-old woman, diagnosed with medullary thyroid carcinoma, was treated with total thyroidectomy and a modified neck dissection in 1999. Two lymph node recurrences in the neck were treated with surgical resection; during surveillance, she developed elevated calcitonin levels, the recurrence site was identified with 18 F-DOPA PET/CT in the liver. Metabolic activity was not associated with a visible lesion in CT, MRI nor ultrasound. Radioguided surgery with 18 F-DOPA allowed an anatomic resection of segments IVb and V., Discussion: In patients with medullary carcinoma and elevated calcitonin during surveillance, 18 F-DOPA PET/CT is an option to evaluate the site of recurrence. Radioguided resection was feasible in this patient, whose hepatic recurrence was not visible with any other imaging method., Conclusion: Radioguided hepatic resection with 18 F-DOPA in metastatic medullary thyroid carcinoma is feasible when the recurrence site is not anatomically identified by any other imaging studies., (Copyright © 2017. Publicado por Elsevier España, S.L.U.)

Background: Total thyroidectomy and cervical lymph node (LN) dissection is generally recommended in patients with medullary thyroid carcinoma (MTC). However, there is no clear evidence for whom to perform prophylactic lateral neck dissection in MTC patients without evident lateral cervical lymph node (LCLN) metastasis in preoperative images. This study evaluated the preoperative features for predicting the LCLN metastasis of MTC., Methods: The study included 26 MTC patients with LCLN metastasis at initial surgery (N1b group) and 47 MTC patients without any LN metastasis or recurrence of disease (N0-NED group). The association between LCLN metastasis and preoperative clinical and sonographic characteristics (size, location, solid component, shape, margin, echogenicity, calcification, and subcapsular location of the tumor) were evaluated., Results: There were no significant differences in age and sex between the N1b and N0-NED groups. Preoperative serum levels of calcitonin >65 pg/mL were associated with LCLN metastasis (p < 0.001). In preoperative neck ultrasonography (US), patients in the N1b group were more commonly found with a larger tumor (>1.5 cm) of irregular shape with a spiculated margin and a subcapsular location than those in the N0-NED group (p = 0.029, p < 0.001, p < 0.001, and p < 0.001, respectively). Increases in the number of these LCLN metastasis-related features were significantly associated with higher risk for LCLN metastasis (p < 0.001). The presence of two or more predictors was an appropriate cutoff point for predicting LCLN metastasis of MTC with 73.1% sensitivity and 91.5% specificity., Conclusions: MTC tumors with high preoperative calcitonin levels (>65 pg/mL), larger size (>1.5 cm), irregular shape, spiculated margins, and subcapsular locations in the neck US are at higher risk for LCLN metastasis. MTC patents with fewer than two predictors might be suitable for treatment without prophylactic LCLN dissection.

Background: Renal medullary carcinoma is a rare renal malignancy of childhood. There are no large series describing the imaging appearance of renal medullary carcinoma in children., Objective: To characterize the clinical and imaging features of pediatric renal medullary carcinoma at initial presentation., Materials and Methods: We retrospectively analyzed images of 25 pediatric patients with renal medullary carcinoma enrolled in the Children's Oncology Group renal tumors classification, biology and banking study (AREN03B2) from March 2006 to August 2016. Imaging findings of the primary mass, and patterns of locoregional and distant spread were evaluated in correlation with pathological and surgical findings., Results: Median age at presentation was 13 years (range: 6-21 years), with a male predominance (3.2:1). The overall stage of disease at initial presentation was stage 1 in 1, stage 2 in 2 and stage 4 in 22. Maximum diameter of the primary renal mass ranged from 1.6 to 10.3 cm (mean: 6.6 cm) with a slight right side predilection (1.5:1). Enlarged (>1 cm short axis) retroperitoneal lymph nodes were identified at initial staging in 20/25 (80%) cases, 10 of which were histologically confirmed while the others did not undergo surgical sampling. Enlarged lymph nodes were also identified in the mediastinum (14/25; 56%) and supraclavicular regions (4/25; 16%). Metastatic disease was present in the lungs in 19/25 (76%) and liver in 6/25 (24%). The pattern of lung metastases was pulmonary lymphangitic carcinomatosis: 10 cases (9 bilateral, 1 unilateral), pulmonary nodules with indistinct margins: 6 cases, pulmonary nodules with distinct margins: 2 cases, while 1 case had pulmonary nodules with both indistinct and distinct margins. Pulmonary lymphangitic carcinomatosis was pathologically confirmed in 4/10 cases. All cases with pulmonary lymphangitic carcinomatosis had associated enlarged mediastinal lymph nodes., Conclusion: Renal medullary carcinoma in children and young adults presents at an advanced local and distant stage in the majority of patients. The diagnosis of renal medullary carcinoma should be considered when a child or young adult presents with a poorly defined/infiltrative, centrally located renal mass, especially in the setting of known sickle cell hemoglobinopathy. Distant metastases are common at initial presentation in the lungs, distant lymph nodes and liver and often involve multiple sites simultaneously. Pulmonary lymphangitic carcinomatosis, a distinctive and uncommon form of lung metastasis in children, is common in this patient population.

Background: Primary analysis of the double-blind, phase III Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM) trial demonstrated significant improvement in progression-free survival with cabozantinib versus placebo in patients with progressive medullary thyroid cancer (MTC). Final analysis of overall survival (OS), a key secondary endpoint, was carried out after long-term follow-up., Patients and Methods: EXAM compared cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomized (2:1) to cabozantinib (140 mg/day) or placebo. Final OS and updated safety data are reported., Results: Minimum follow-up was 42 months. Kaplan-Meier analysis showed a 5.5-month increase in median OS with cabozantinib versus placebo (26.6 versus 21.1 months) although the difference did not reach statistical significance [stratified hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.64-1.12; P = 0.24]. In an exploratory assessment of OS, progression-free survival, and objective response rate, cabozantinib appeared to have a larger treatment effect in patients with RET M918T mutation-positive tumors compared with patients not harboring this mutation. For patients with RET M918T-positive disease, median OS was 44.3 months for cabozantinib versus 18.9 months for placebo [HR, 0.60; 95% CI, 0.38-0.94; P = 0.03 (not adjusted for multiple subgroup analyses)], with corresponding values of 20.2 versus 21.5 months (HR, 1.12; 95% CI, 0.70-1.82; P = 0.63) in the RET M918T-negative subgroup. Median treatment duration was 10.8 months with cabozantinib and 3.4 months with placebo. The safety profile for cabozantinib remained consistent with that of the primary analysis., Conclusion: The secondary end point was not met in this final OS analysis from the trial of cabozantinib in patients with metastatic, radiographically progressive MTC. A statistically nonsignificant increase in OS was observed for cabozantinib compared with placebo. Exploratory analyses suggest that patients with RET M918T-positive tumors may experience a greater treatment benefit with cabozantinib., Trial Registration Number: NCT00704730., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. [br]All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Although advanced thyroid carcinoma patients who cannot be cured by conventional therapy have lacked effective treatment, multitargeted tyrosine kinase inhibitors have recently become available. Phase 3 trials of lenvatinib showed a median time to objective response of 2 (95 % confidence interval (CI) 1.9-3.5) months, demonstrating that shrinks tumors rapidly. The phenomenon of immediate tumor shrink is known as early tumor shrinkage (ETS) which is related to clinical outcome in other malignancies. However, precisely when within 8 weeks lenvatinib starts to affect tumors remains unclear. In tumors near the carotid arteries, trachea, or esophagus, a rapid therapeutic effect can induce fistula formation or arterial bleeding. To prevent such treatment-emergent serious adverse events (SAE), early imaging evaluation seems to be very important. In this study, the point in time when lenvatinib started to shrink tumors was retrospectively investigated. The subjects were 16 patients who started lenvatinib administration between May and August 2015. Tumor size was evaluated by computed tomography (CT) scans frequently within the first 8 weeks according to the Response Evaluation Criteria In Solid Tumors (RECIST) guideline. Initial tumor response was defined as ≥ 10% tumor reduction. Serum thyroglobulin (Tg) level was monitored in 8 differentiated thyroid carcinoma (DTC) without TgAb patients. At the first evaluation, 13 patients (83.3 %) showed tumor reduction and that decreased with time. Thirteen patients (83.3 %) showed >10 % tumor reduction within 8 weeks. In all DTC patients, serum Tg level was markedly decreased. In conclusion, lenvatinib immediately shrinks tumors, the so-called ETS phenomenon. Therefore, careful attention should be paid to fistula formation from the early phase.

Intraoperative frozen section (FS) can be reduced during thyroid lobectomy according to the results of fine needle aspiration (FNA). We evaluated the role of intraoperative FS in thyroid nodules with different diagnostic categories of the Bethesda System for Reporting Thyroid Cytopathology by FNA. This retrospective study included 1,235 nodules collected via thyroidectomy with both preoperative FNA and intraoperative FS at the Second Affiliated Hospital of Zhejiang University School of Medicine, from January 2011 to January 2014. FNA cytological diagnosis was classified into six categories, based on the Bethesda system. The diagnostic findings of FNA cytology and FS histology were compared with the final histological results. 189 nodules were benign. The remainder were malignant. FS diagnosis was more accurate than FNA diagnosis for nodules classified as Bethesda Categories II, III, and IV (P < 0.05). However, the accuracy of FNA diagnosis in nodules assigned Bethesda Categories V and VI was significantly higher than that of FS (P < 0.05). FS appears be beneficial for thyroid nodules classified as Bethesda categories I through IV. FS may not be necessary in nodules diagnosed as Bethesda Categories V and VI.

Background: Familial non-medullary thyroid cancer (FNMTC) mandates family screening with ultrasound; however, the need for screening paediatric thyroid cancer with no family history has not been addressed., Methods: This study conducted a retrospective cohort study in a tertiary hospital. The study group is composed of patients ≤18 years undergoing surgery for papillary thyroid cancer (PTC) from 2008 to 2014., Results: During the study period, 15 paediatric patients had PTC. Only one patient had a prior family history of PTC involving two second-degree relatives. Of the 30 parents, four were lost to follow-up, with the remaining 26 undergoing screening thyroid ultrasound. Nodular thyroid disease was documented in eight ultrasounds performed. Subsequently, one has not undergone fine-needle biopsy, five were benign and two underwent surgical resection: one having a benign follicular adenoma and the other a papillary microcarcinoma with nodal micrometastasis., Conclusions: Routine ultrasound screening of parents of children presenting with PTC and no family history do not demonstrate an increased incidence of FNMTC. Screening of affected families is likely to demonstrate the expected background incidence of nodular thyroid disease and incidental papillary microcarcinoma. As such, it is unlikely to be useful., (© 2015 Royal Australasian College of Surgeons.)

Purpose: The aim of this study was to assess therapeutic response to breast cancer neoadjuvant chemotherapy (NAC) by F-FDG positron emission mammography (PEM) compared with that to whole-body F-FDG PET (WBPET)., Methods: Twenty patients underwent WBPET and PEM 3 times: the first time was before NAC, the second time was after 2 courses of NAC, and the third time was after all courses of NAC. A pathological complete response (pCR) was defined as no evidence of residual invasive cancer with or without ductal carcinoma in situ. The relationships between each modality's SUVmax and pathological response were evaluated., Results: Nine patients achieved a pCR, whereas the other 11 patients had a non-pCR. The SUVmax of WBPET after 2 courses of NAC was significantly lower in the pCR group than in the non-pCR group (1.4 ± 0.4 vs 2.7 ± 2.1, P = 0.0334). There were no significant differences in the SUVmax of PEM (ie, PEM uptake value [PUV]) between the groups. The SUVmax of WBPET (area under the ROC curve [AUC] = 0.761) was superior to the PUVmax (AUC, 0.648) for predicting non-pCR at the interim time point. After all courses of chemotherapy, there were no significant differences between the groups in the SUVmax of WBPET; however, PUVmax was significantly lower in the pCR group than in the non-pCR group (1.0 ± 0.2 vs 2.5 ± 2.7, P = 0.0351). After NAC, the PUVmax (AUC, 0.796) was superior to the SUVmax of WBPET (AUC, 0.671)., Conclusions: There proved to be no apparent superiority of PEM in predicting pCR at the interim time point. Positron emission mammography had greater diagnostic capability for detecting residual cancer after all courses of NAC.

This study was designed to retrospectively compare the sonographic features of medullary thyroid carcinoma (MTC) and the features of papillary thyroid carcinoma (PTC).A total of 97 patients with 127 MTCs between January 2000 and January 2016 and 107 consecutive patients with 132 PTCs were included in this study. Two radiologists retrospectively determined the sonographic features and compared the findings of MTCs and PTCs.Compared with the patients with PTCs, the patients with MTCs were older (46.9 years vs 42.9 years, P = 0.016) and the male proportion was higher (53.6% vs 33.6%, P = 0.005). Most of the MTCs had an irregular shape (72.4%), a length/width ratio <1 (75.6%), an unclear boundary (63.8%), no peripheral halo ring (93.7%), hypoechogenicity (96.9%), heterogeneous echotexture (76.4%), no cystic change (78.7%), calcification (63.8%), and hypervascularity (72.4%). There was no significant difference in the boundary, peripheral halo ring, echogenicity, and calcification between the MTCs and PTCs. However, compared with the PTCs, a larger size (2.2 vs 1.2 cm, P <0.001), a regular shape (27.6% vs 7.6%, P <0.001), a length/width ratio <1 (75.6% vs 51.5%, P<0.001), heterogeneous echotexture (76.4% vs 54.5%, P <0.001), cystic change (21.3 vs 8.3%, P = 0.005), and hypervascularity (72.4% vs 47.7%, P <0.001) were more frequent in the MTCs.The sonographic features with a higher likelihood of malignancy are common in MTCs, including a shape taller than the width, irregular infiltrative margins, an absent halo, hypoechogenicity, the presence of microcalcifications, and increased intranodular vascularity. However, MTCs tend to possess these suspicious sonographic features less often than PTCs, with the exception of hypervascularity, which was more frequent in MTCs., Competing Interests: The authors have no conflicts of interest to disclose.

Background: The 2015 American Thyroid Association (ATA) thyroid nodule guidelines recommend selecting nodules for biopsy based on a sonographic pattern classification. These patterns were developed based on features of differentiated thyroid cancer. This study aimed to evaluate the performance and the inter-observer agreement of this classification system in medullary thyroid carcinoma (MTC)., Methods: The medical records of all patients with MTC evaluated at the authors' institution between 1998 and 2014 were retrospectively reviewed. Only patients with presurgical thyroid ultrasound available for review were included in the study. Five independent reviewers assessed the stored ultrasound images for composition, echogenicity, margins, presence of calcifications, and extrathyroidal extension for each nodule. The presence of suspicious lymph nodes was also evaluated when presurgical lateral neck ultrasound was available for review. Each nodule was classified according to the ATA sonographic patterns. Inter-observer agreement was calculated for each sonographic feature and for the sonographic patterns. To validate the findings, a systematic review of the literature and meta-analysis on the sonographic features of MTC was conducted., Results: In this institutional cohort, the inter-observer agreement for individual sonographic features was moderate to good (κ = 0.45-0.71), and for the ATA classification it was good (κ = 0.72). Ninety-seven percent (29/30) of the MTCs were classified in the intermediate or high suspicion patterns. A total of 249 MTCs were included in the meta-analysis. Based on pooled frequencies for solid composition and hypoechogenicity, >95% of MTCs would be classified at least in the intermediate suspicion pattern, warranting the lowest-size threshold for biopsy (≥1 cm)., Conclusions: The sonographic patterns proposed by the ATA perform well in MTC, and inter-observer agreement is good to very good.

Many open questions remain to be elucidated about the diagnosis, treatment and prognosis of medullary thyroid cancer (MTC). The most intriguing concerns the outcome of MTC patients after surgery. Great importance is usually given to serum calcitonin (Ct) and carcinoembryonic (CEA) levels. It is commonly believed that the higher are the levels of these tumor markers and their kinetics (double time and velocity of markers levels) the worst is the prognosis. However, this is not the rule, as there are huge MTC metastatic deposits characterized by low serum Ct and CEA levels, and this condition is not closely related to the outcome of the disease during post-surgical follow-up. A series is reported here of patients who have these characteristics, as well as a description of their prognosis and clinical outcome., (Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.)

Background and Objectives: Preoperative axillary ultrasound (AUS) in clinically node-negative patients may increase axillary lymph node dissection (ALND) in ACoSOG Z0011-eligible patients. We hypothesize that AUS identifies operative axillary disease (>3 positive nodes) in women undergoing breast conserving surgery (BCS)., Methods: After IRB approval, a retrospective review of female breast cancer patients was performed; patients with clinical T1/T2 tumors undergoing BCS were included. Clinical, radiologic, and pathologic data were collected., Results: Of 139 eligible subjects, 119/139 (86%) had nonpalpable axillary nodes. 47/119 patients (40%) had abnormal AUS and 15/47 (32%) had a positive FNA. Fourteen had ALND ;10/14 (71%) had >3 positive nodes. 6/32 (18%) with abnormal AUS but FNA negative were sentinel lymph node (SLN) positive. Of 72 normal AUS, 15 (22%) were SLN positive; 9/15 (60%) had ALND; 1 (11%) had >3 positive nodes. When evaluating for >3 positive nodes, AUS plus FNA had a sensitivity of 91%, specificity of 95%, NPV of 99%, and PPV of 71%., Conclusions: AUS/FNA has a high NPV for axillary metastasis and remarkable sensitivity for three or more positive axillary nodes, therefore AUS-identified metastasis should be treated as clinically node-positive disease, and is appropriate even in patients planning breast conserving surgery., (© 2015 Wiley Periodicals, Inc.)

Renal medullary carcinoma (RMC) is a rare tumor, originating in the epithelial papillary cells, that primarily affects young black men with sickle cell trait. We report the case of a 29-year-old Caucasian woman, who at ultrasound showed a cystic mass at the right kidney, with a vascular pattern at the level of the cystic wall. A CT-guided biopsy of the lesion was performed, revealing the presence of unspecified tumor cells. A total nephrectomy was then performed. Microscopically, a tumor resulting from the epithelial papillary cells was observed; several areas of lymphoplasmacytic infiltrates were seen at the junction between the normal kidney tissue and the tumor, and a renal medullary carcinoma was diagnosed. Six months later, the patient developed multiple pulmonary metastases and started chemotherapy with Carboplatin, Paclitaxel and Gemcitabine. The patient died after 27 months of follow-up.RMC is a tumor that usually occurs in young black men, at an average age of 25 years with extremes of 11 and 39 years. Sickle-cell disease or sickle-cell trait is often present. The longest documented survival (until now) for RMC was 16 months. The best treatment is surgery with enlarged nephrectomy. There are still no appropriate chemotherapy protocols.

Objective: Medullary carcinoma of the thyroid (MTC) is a rare neuroendocrine tumour (NET) that expresses somatostatin receptors on the cell membrane and secretes calcitonin. Surgery is the primary curative modality but is achieved only when the diagnosis is timely so there is a high rate of persistent and recurrent disease indicated by a rise in the serum calcitonin levels. Successful management of recurrent disease requires accurate localisation with cross sectional and functional imaging. The introduction of gallium-68-Dotatate ((68)Ga-Dotatate) peptides positron emission tomography/computerized tomography (PET/CT) has significantly improved the detection of NET and has been reported as a valuable adjunct in MTC localisation. We retrospectively reviewed our cases of MTC to correlate the detectability of (68)Ga-Dotatate in relation to calcitonin levels and assess suitability of inoperable patients for peptide receptor radionuclide therapy (PRRT)., Subjects and Methods: Seven patients (age range 31-66 years, M:F 3:4) with raised calcitonin (mean=7,143pg/mL) were referred for (68)Ga-Dotatate PET/CT scan for localisation of persisting recurrent MTC. Six patients were known to have MTC treated with thyroidectomy and one patient was presenting for the first time. All patients had multiple imaging including ultrasound (US), CT, magnetic resonance imaging (MRI), fluorine-18-fluorodeoxyglucose ((18)F-FDG) PET/CT and iodine-123-metaiodobenzylguanidine ((123)I-MIBG). Positive findings were defined as areas of increased uptake other than the organs of normal distribution and were correlated with results of biopsies, other imaging, long term monitoring of calcitonin and clinical follow up., Results: In 6/7 patients with very high serum calcitonin (range= 672-37,180, mean=8,320pg/mL) (68)Ga-Dotatate PET/CT confirmed the presence of active disease seen on other modalities or detected hitherto unsuspected lesions. In at least 3 cases, (68)Ga-Dotatate PET/CT showed many more lesions compared to other imaging combined. In 1/7 patient (68)Ga-Dotatate PET/CT was negative in line with a relatively low calcitonin level (80pg/mL) and negative disease on fine needle aspiration., Conclusion: (68)Ga-Dotatate PET/CT is an effective tool for localising metastatic spread of MTC. It appears to be most effective in the presence of higher levels of serum calcitonin, probably in excess of 500pg/mL. The results of our small cohort had an impact on staging and management with the introduction of peptide receptor radionuclide therapy for inoperable disease.

Purpose: To evaluate the malignancy risks of thyroid nodules with nondiagnostic results at ultrasonography (US)-guided fine-needle aspiration biopsy ( FNAB fine-needle aspiration biopsy ) and the criteria for selecting those for repeat US-guided FNAB fine-needle aspiration biopsy according to the thyroid imaging reporting and data system ( TIRADS thyroid imaging reporting and data system )., Materials and Methods: This retrospective study was approved by the institutional review board, and the requirement to obtain informed consent was waived. Five hundred forty-eight nondiagnostic nodules were included. US features of internal composition, echogenicity, margin, calcifications, shape, and vascularity were evaluated, and thyroid nodules were classified according to TIRADS thyroid imaging reporting and data system . TIRADS thyroid imaging reporting and data system category 3 included nodules without any suspicious features of solidity, hypoechogenicity or marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, and taller-than-wide shape. Categories 4a, 4b, 4c, and 5 included nodules with one, two, three or four, or five suspicious US features. The malignancy risk was calculated., Results: Of the 548 nodules, 40 (7.3%) were malignant and 508 (92.7%) were benign. The malignancy risks of categories 3 and 4a nodules were 0.8% and 1.8%, respectively, whereas the malignancy risks of categories 4b, 4c, and 5 nodules were 6.1%, 14.4%, and 31%. In the 294 nodules larger than 10 mm, the malignancy risks of categories 3, 4a, 4b, 4c, and 5 nodules were 0.9%, 1.3%, 0%, 15%, and 33%, respectively. In the 254 nodules measuring 10 mm or smaller, the malignancy risks of categories 3, 4a 4b, 4c, and 5 nodules were 0%, 2.7%, 14%, 14.3%, and 31%., Conclusion: Nondiagnostic thyroid nodules without suspicious US features and those with one suspicious feature can be followed up with US, but nondiagnostic nodules with two or more suspicious features should undergo repeat US-guided FNAB fine-needle aspiration biopsy.

Aim: The American thyroid association (ATA) recommends that additional imaging procedures supplement cervical ultrasonography (US) in any patient with a basal calcitonin value above 150 pg/ml in the follow-up of medullary thyroid carcinoma (MTC). The aim of the present study was to reaffirm or challenge this cut-off for 18-Fluorine-Fluorodihydroxyphenylalanine positron emission tomography (18F-DOPA PET) and conventional imaging ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI))., Materials and Methods: Thirty-nine patients (18 females, 21 males), mean age 62 years, range from 35 to 86, followed-up for MTC were included in the present retrospective study. In our patients 64 18F-DOPA scans, 28 neck US, 28 CT and 8 MRI were performed. For all cases basal calcitonin values were available. Sensitivity and specificity of 18F-DOPA PET and conventional imaging (US, CT, MRI) related to calcitonin values were calculated., Results: According to the calcitonin cut-off of 150 pg/ml, we found the following sensitivities and specificities: 79% and 80% for 18F-DOPA PET, 75% and 92% for US, 80% and 25% for CT, 50% and 75% for MRI. Taking the level of detectable calcitonin, we calculated the following sensitivities: 52% for 18F-DOPA PET, 46% for US, 79% for CT and 38% for MRI., Conclusion: We cannot confirm the calcitonin cut-off proposed by the ATA for the detection of MTC recurrences and contemporaneously we cannot state that 18F-DOPA PET has a very high sensitivity. For the neck region 18F-DOPA PET and US showed similar results. 18F-DOPA PET/CT seems to be the best imaging modality for whole-body tumor detection. Bone metastases are best detected by MRI., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Metastasis to the primary thyroid carcinoma is extremely rare. We report here a case of colonic adenocarcinoma metastasis to medullary thyroid carcinoma in a 53-yr old man with a history of colon cancer. He showed a nodular lesion, suggesting malignancy in the thyroid gland, in a follow-up examination after colon cancer surgery. Fine needle aspiration biopsy (FNAB) of the thyroid gland showed tumor cell clusters, which was suspected to be medullary thyroid carcinoma (MTC). The patient underwent a total thyroidectomy. Using several specific immunohistochemical stains, the patient was diagnosed with colonic adenocarcinoma metastasis to MTC. To the best of our knowledge, the present patient is the first case of colonic adenocarcinoma metastasizing to MTC. Although tumor-tumor metastasis to primary thyroid carcinoma is very rare, we still should consider metastasis to the thyroid gland, when a patient with a history of other malignancy presents with a new thyroid finding.

Purpose: PET is a powerful tool for assessing targeted therapy. Since (18)F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated (18)F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial., Methods: Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic value of the PET response was compared with demographic parameters at inclusion including age, sex, RET mutation, time from initial diagnosis, calcitonin and CEA concentrations and doubling times (DT), SUVmax, location of disease and bone marrow involvement, and with response using RECIST, biomarker concentration variation, impact on DT, and combined methods., Results: Enrolled in the study were 25 men and 17 women with disease progression. The median OS from pRAIT was 3.7 years (0.2 to 6.5 years) and from MTC diagnosis 10.9 years (1.7 to 31.5 years). After pRAIT, PET/CT showed 1 patient with a complete response, 4 with a partial response and 24 with disease stabilization. The combined evaluation showed 20 responses. For OS from pRAIT, univariate analysis showed the prognostic value of biomarker DT (P = 0.011) and SUVmax (P = 0.038) calculated before pRAIT and impact on DT (P = 0.034), RECIST (P = 0.009), PET (P = 0.009), and combined response (P = 0.004) measured after pRAIT. PET had the highest predictive value with the lowest Akaike information criterion (AIC 74.26) as compared to RECIST (AIC 78.06), biomarker variation (AIC 81.94) and impact on DT (AIC 79.22). No benefit was obtained by combining the methods (AIC 78.75). This result was confirmed by the analysis of OS from MTC diagnosis., Conclusion: (18)F-FDG PET appeared as the most potent and simplest prognostic method to predict survival in patients with progressive MTC treated with pRAIT. Biomarker DT before pRAIT also appeared as an independent prognostic factor, but no benefit was found by adding morphological and biomarker evaluation to PET assessment.

Background: The indications of repeat fine-needle aspiration (FNA) for thyroid nodules with benign results of the Bethesda system were investigated., Methods: A total of 1,398 nodules were classified according to the Thyroid Imaging Reporting and Data System (TIRADS). TIRADS category 3 included nodules without solidity, hypoechogenicity or marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, and taller-than-wide shape on ultrasonography (US). Categories 4a, 4b, 4c, and 5 included nodules with one, two, three or four, or five suspicious US features, respectively. The malignancy risks, and odds ratio (OR) with 95 % confidence interval (CI) were calculated. Analyses were performed for all nodules, nodules >10 mm, and nodules ≤10 mm., Results: Of 1.398 nodules, 43 (3.1 %) were malignanct. The malignancy risks of benign nodules with categories 3, 4a, and 4b were 0.7, 1.2, and 0.7 %, respectively, whereas those for nodules with categories 4c and 5 were 9.8 and 22.2 %, respectively. The ORs of nodules with categories 4c and 5 were 19.4 (95 % CI 5.0-76.2) and 50.6 (95 % CI 10.4-245.0), respectively. In nodules >10 mm, the malignancy risks of categories 4c and 5 were 2.7 and 20 %, respectively, and the ORs were 10.7 (95 % CI 1.2-93.7) and 236.1 (95 % CI 12.6-4426.4), respectively. In nodules ≤ 10 mm, the malignancy risks of categories 4c and 5 were 12.6 and 22.6 %, respectively, and the ORs were 10.1 (95 % CI 1.3-78.0) and 18.9 (95 % CI 2.1-168.9), respectively., Conclusions: Repeat US-guided FNA should be considered in benign thyroid nodules with three or more suspicious US features regardless of size.

To investigate whether further, diagnostic procedures should be recommended in patients with slight increase of preoperative serum basal calcitonin (bCT) levels in whom surgical treatment can be recommendable. Fourteen consecutive patients with nodular thyroid disease underwent thyroidectomy in our center for suspected medullary thyroid microcarcinoma (MTC) because their serum bCT levels were slightly higher than the upper limit of normal range. Serum bCT was measured by radioimmunoassay, normality range = 0-20 ng/L. Surgical specimens were examined by the same pathologist using histologic and immunohistochemistry techniques. An extensive search for parafollicular C-cell hyperplasia (CCH) and/or microscopic MTC foci was performed. At preoperative ultrasound, a single thyroid nodule was depicted in three patients while a multinodular goiter in 11. The bCT values ranged between 24.4 and 94.6 ng/L, median 42.2 ng/L while the pentagastrin-stimulated CT (sCT) values by pentagastrin test ranged between 61.5 and 1,262 ng/L, median 245.0 ng/L. Total thyroidectomy was performed in 13 patients, and lobectomy in the other one; central node dissection was also performed in eight cases. At histology, MTC was diagnosed in nine patients (64.3 %), showing a median maximum diameter of 6.1 mm (range, 1.5-17 mm); CCH was diagnosed in the other five patients (35.7 %). The pentagastrin stimulation test was obtained in all patients. It is worth noting that a very high increase of sCT >100 ng/mL was observed in 5/9 patients with MTC and in 2/4 patients with HCC, therefore suggesting the absence of a relationship between the entity of response to pentagastrin test with a specific pathology (MTC vs. HCC). In six patients, the MTC was the nodule on which preoperative FNAC had been performed, while in other three patients preoperative FNAC had been performed on a different nodule from the MTC. Based on our experience, in case of the pentagastrin stimulation test with sCT <100 ng/L and a single nodule, the CT assay on FNAC may be useful, subsequently lobectomy with definitive histological diagnosis is recommended. In case of the Pg test with sCT <100 ng/L and bilateral goiter, total thyroidectomy with histological diagnosis is recommended. In this way, as for the surgical procedure, total thyroidectomy is recommended in cases of bilateral goiter, while lobectomy can be offered for cases with single nodes with serum dosage of bCT in the strict follow up. In case of the pentagastrin stimulating test with sCT <100 ng/L and bilateral goiter, total thyroidectomy with histological diagnosis is recommended.

Introduction: Thyroid nodular goitre is one of the most common endocrine disorders. Differentiating between benign and malignant lesions is an emerging challenge in endocrinological practice. Ultrasonography (US) remains the most commonly applied method in the preliminary assessment of lesions and is the basis for the decision as to fine needle aspiration biopsy (FNAB) and further diagnostics. Many studies have evaluated the diagnostic value of US malignancy features. However, they focused mainly on papillary thyroid cancer (PTC). It remains unclear whether other types of thyroid carcinoma (TC) are also characterised by the same US features. The aim of this study was to assess the usefulness of US features considered as markers in the diagnosis of medullary thyroid cancer (MTC)., Material and Methods: The PubMed/MEDLINE and Cochrane Library databases were searched to identify studies on US features of MTCs. The random-effects model was used to calculate pooled sensitivity and specificity and odds ratios (OR) - if a comparison with PTCs was available., Results: Hypoechogenicity was present in 83.4% of MTCs, and 32.7% were markedly hypoechogenic. None of the 157 MTCs was hyperechogenic. Sensitivity of halo absence was 88.9%, but irregular margins were present in 38.0%. 35.5% of MTCs had microcalcifications, and 27.0% had macrocalcifications. 14.4% presented 'taller than wide feature' (higher anteroposterior than transverse diameter). Apart from macrocalcifications, all these features occurred insignificantly less often in MTCs than in PTCs., Conclusions: US features commonly considered as markers of malignancy can be useful also in the diagnostics of MTCs. However, MTCs tend to possess suspicious US features slightly less often than PTCs. Some features, such as hyperechogenicity, can be considered to be strong markers of benign status. Although the US appearance of the thyroid lesion is an important diagnostic factor, it is worth remembering that it does not allow for a definitive differentiation between benign and malignant nodules. In the case of MTCs, as well as other TCs, US examination remains a valuable diagnostic tool, but should always be interpreted carefully in the context of other examinations.

Background: Our aim through this study was to develop a statistical tool to quantify risk of malignancy in thyroid nodules based on clinical, biochemical, and ultrasound features, which could be used to select which nodules require ultrasound-guided fine-needle aspiration., Methods: Clinical records, biochemical profiles, pathology reports, and ultrasound images were reviewed. Multivariate logistic regression was used to rank variables in their ability to predict malignancy., Results: In all, 190 nodules were reviewed. The final diagnoses were papillary carcinoma in 105 patients (66%), other carcinoma in 8 patients (5%), and benign thyroid pathology in 45 patients (29%). After exclusions, 182 nodules remained for analysis on a per nodule basis. The 8 variables with highest predictive value were: age; thyroid-stimulating hormone; and ultrasound size, shape, echo texture, calcification, margin, and vascularity. The nomogram had a concordance index of 75%., Conclusion: We produced a nomogram able to accurately predict the need to perform ultrasound-guided fine-needle aspiration on a thyroid nodule based on biochemical, clinical, and ultrasound features., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: To evaluate a second-generation assay for basal serum calcitonin (CT) measurements compared with the pentagastrin-stimulation test for the diagnosis of inherited medullary thyroid carcinoma (MTC) and the follow-up of patients with MTC after surgery. Recent American Thyroid Association recommendations suggest the use of basal CT alone to diagnose and assess follow-up of MTC as the pentagastrin (Pg) test is unavailable in many countries., Design: Multicentric prospective study., Patients: A total of 162 patients with basal CT <10 ng/l were included: 54 asymptomatic patients harboured noncysteine 'rearranged during transfection' (RET) proto-oncogene mutations and 108 patients had entered follow-up of MTC after surgery., Measurement: All patients underwent basal and Pg-stimulated CT measurements using a second-generation assay with 5-ng/l functional sensitivity., Results: Ninety-five per cent of patients with basal CT ≥ 5 ng/l and 25% of patients with basal CT <5 ng/l had a positive Pg-stimulation test (Pg CT >10 ng/l). Compared with the reference Pg test, basal CT ≥ 5 ng/l had 99% specificity, a 95%-positive predictive value but only 35% sensitivity (P < 0.0001). Overall, there were 31% less false-negative results using a 5-ng/l threshold for basal CT instead of the previously used 10-ng/l threshold., Conclusion: The ultrasensitive CT assay reduces the false-negative rate of basal CT measurements when diagnosing familial MTC and in postoperative follow-up compared with previously used assays. However, its sensitivity to detect C-cell disease remains lower than that of the Pg-stimulation test., (© 2012 Blackwell Publishing Ltd.)

Aim: To evaluate the efficacy and clinical impact of the FDG-PET in the diagnosis of suspicion of recurrence of medullary thyroid cancer (MTC) in patients with elevated serum calcitonin and negative imaging test., Material and Methods: We performed a retrospective study of 31 consecutive cases from february 2001 to october 2007 of 17 women and 14 men, mean age 56.2 years (range: 26-88), with anatomical-pathology diagnosis of medullary thyroid cancer and suspicion of recurrence due to abnormal elevation of calcitonin and negative imaging tests. All of the patients underwent whole body FDG-PET scan with a dedicated PET or PET-CT 60 minutes after intravenous injection of 333-434 MBq of (18)F-FDG. Results were confirmed by pathology study in 45.2% of the patients and by clinical follow-up with a mean of 4 years (range: 16 m-8 years), Results: Sensitivity was 88%, specificity 84.6%, positive predictive value 88%, negative predictive value 84.6% and diagnostic accuracy 87%. The results of the FDG PET modified the therapeutic strategy in 14 cases (45.2%). A comparison was made of the mean values of calcitonin using the Student's "t" test between positive PET studies for the disease and negative ones. No significant differences were found (P=.3)., Conclusions: In patients with MTC and suspected recurrence with elevated calcitonin and negative imaging test, the FDG is the best test for the diagnosis of occult recurrence in MTC with elevated calcitonin and negative imaging techniques with elevated clinical impact. It facilitates the therapeutic management of the patients with MTC recurrence, and should be included in the diagnosis algorithm in these patients., (Copyright © 2011 Elsevier España, S.L. y SEMNIM. All rights reserved.)

Medullary thyroid cancer (MTC) arises from parafollicular C cells and is an elusive tumor to image. It occurs as a sporadic neoplasm in 70-80% of cases and is hereditary in 20-30% because of germline mutations of the rearranged during transfection proto-oncogene. Successful disease management relies on accurate staging. Tumor secretory biomarkers are highly sensitive to a disease; however, despite a wide variety of radiopharmaceuticals for molecular imaging that take advantage of hybrid SPECT/CT and PET/CT fusion imaging, imaging of MTC is still problematic. After initial surgical resection, the limited sensitivity of localization of small locoregional disease and the inability to detect early liver metastases hamper the success of later surgical approaches. F-fluorodeoxyglucose PET has been used to detect MTC recurrences with modest success and may be best suited for only a small subset of more biologically aggressive MTCs. Recent developments in PET imaging with novel radiopharmaceuticals targeting specific cellular processes of MTC offer increased sensitivity for identifying recurrence, assessing prognosis, and guiding selection of optimal therapies.

The aim of this study was to determine whether early acquisition of F-fluorodihydroxyphenylalanine (F-FDOPA) PET/CT could improve the detection of medullary thyroid cancer (MTC). We retrospectively compared early (median time: 15 min) and delayed (median time: 94 min) acquisitions, positive on at least one of the two phases, in 15 dual-phase F-FDOPA PET/CT examinations performed on 14 patients referred for initial staging (one examination), suspected recurrence (eight examinations) or restaging of MTC (six examinations). Among the 14 true-positive (TP) examinations, more lesions (51 vs. 43) or more intense uptake (mean SUVmax=4 vs. 2.4, P<0.05) was observed on early versus delayed phases, regardless of the anatomical site of disease (lymph node, liver or bone). The only false-positive case, a reactive lymph node, was visible only on the delayed acquisition. Early acquisition appeared to be more appropriate in the detection of MTC lesions compared with acquisition at 60 min or later.

Objective: To prospectively evaluate the role of Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI-octreotide (Ga-DOTA-NOC) PET-CT in patients with recurrent medullary thyroid carcinoma (MTC) and compare the same with F-fluorodeoxyglucose (F-FDG) PET-CT., Materials and Methods: Fifty-two consecutive patients with recurrent MTC based on raised serum calcitonin levels underwent Ga-DOTA-NOC PET-CT. In addition, 41 patients also underwent F-FDG PET-CT. PET-CT images were evaluated by two experienced nuclear medicine physicians both qualitatively and quantitatively (standardized uptake value). Histopathology (when available), correlation with conventional imaging modalities (ultrasonography/CT/MRI) and subsequent clinical/imaging follow-up were used as reference standard. Serum calcitonin levels were correlated with findings of PET-CT., Results: Overall, Ga-DOTA-NOC PET-CT showed a sensitivity of 80.7% [95% confidence interval (CI) 67.4-90.3] and a positive predictive value of 100% (95% CI 91.5-100) for detecting recurrent MTC. When both were available (n=41), Ga-DOTA-NOC PET-CT proved superior to F-FDG PET-CT with a higher sensitivity (75.61 vs. 63.4%). However, the difference was statistically not significant (P=0.179). Ga-DOTA-NOC PET-CT was superior to F-FDG PET-CT for detecting recurrence in cervical lymph nodes (P<0.001). Both modalities were concordant in 75% of cases. No significant cut-off level of calcitonin could be derived for either Ga-DOTA-NOC or F-FDG PET-CT., Conclusion: Both Ga-DOTA-NOC PET-CT and F-FDG PET-CT are able to localize disease recurrence in patients with MTC, and their role appears to be complementary for this purpose.

Background: Thyroid cancer cells have been shown to take up (99m)Tc-sestamibi. The role for (99m)Tc-sestamibi scintigraphy (Tc-MIBI) in the diagnosis of thyroid cancer in patients with primary hyperparathyroidism (PHPT) is unclear. Our aim was to determine whether dual-isotope parathyroid scintigraphy is useful in identifying thyroid cancer., Methods: A prospective database of 3,187 patients who underwent neck exploration for PHPT was reviewed to identify patients who had concurrent thyroid resection. Patients with benign and malignant thyroid disease were comparatively analyzed., Results: A total of 470 patients underwent both thyroidectomy and parathyroidectomy (reoperations in 21%). Benign disease (n = 391, 83%) was more common than malignancy [papillary thyroid cancer (n = 75) and medullary thyroid cancer (n = 5); 1 had both]. Dual-isotope scintigraphy obtained in 374 patients (80%) had a sensitivity of 67% and a positive predictive value of 66% for parathyroid adenoma localization in these patients with thyroid disease. False-positive scintigraphy occurred in 22% with benign and 45% with malignant thyroid disease (P = 0.002). On Tc-MIBI imaging, 54 (86%) of 63 patients with malignancy had hot nodules, compared to 248 (81%) of 308 patients with benign disease (P = 0.49). On I-123 imaging, 34 (54%) of 63 patients with malignancy had cold nodules, compared to 42 (14%) of 304 patients with benign disease (P < 0.001). A dual-isotype phenotype of both Tc-MIBI-Hot and I-123-Cold had sensitivity 52%, specificity 88%, positive predictive value 47%, and negative predictive value 90% for detecting a thyroid malignancy., Conclusions: A Tc-MIBI-Hot/I-123-Cold phenotype is very specific for detecting thyroid malignancy. Patients with this imaging phenotype should strongly be considered for preoperative ultrasound-guided biopsy. Patients found intraoperatively to have false-positive parathyroid scintigraphy should be evaluated for thyroid cancer.