Recurrent Medullary Thyroid Carcinoma Research Articles

Feasibility and therapeutic potential of the 68Ga/177Lu-DOTATATE theranostic pair in patients with metastatic medullary thyroid carcinoma

BackgroundThis study assessed: 1) the clinical efficacy of imaging with 68Ga-DOTATATE PET/CT (SSTR (somatostatin receptor)-PET) to detect medullary thyroid carcinoma (MTC); and 2) the therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE in MTC patients. Materials and methodsPatients with histologically proven MTC and suspected recurrence following thyroidectomy, based on raised serum calcitonin levels, underwent SSTR-PET. In addition, to evaluate the clinical efficacy and safety of PRRT, the patients with intense uptake on SSTR-PET or 99mTc-octreotide scintigraphy underwent PRRT. The Common Terminology Criteria for Adverse Events (version 4.03) was used to grade adverse events after PRRT. Treatment response was classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). ResultsTwenty MTC patients (10 male, 10 female) with a median age of 48.5 years underwent SSTR-PET. SSTR-PET was positive in 17/20 patients (85%). Four of the 17 patients with positive SSTR-PET were scheduled for PRRT. In addition, 2 patients had positive 99mTc-octreotide scintigraphy results (Krenning score ≥ 2) and were scheduled for PRRT. Two of the 6 patients who underwent PRRT showed PR, 2 SD and 2 PD. Two patients died during the follow-up period. Median overall survival was 19 months (95% CI: 5.52–29.48). There were no cases of significant toxicity. ConclusionRadiolabeled somatostatin analogs are contributive for the management of recurrent MTC. 68Ga-DOTATAE PET-CT showed a relatively high detection rate in recurrent MTC. In addition, PRRT with 177Lu-DOTATATE was found to be a safe alternative therapeutic option for MTC.

Abstract #1182766: Ectopic ACTH Secretion from Recurrent Medullary Thyroid Carcinoma

On some occasions, medullary thyroid carcinoma (MTC) can be associated with the production of several substances capable of causing different syndromes of hormonal excess, and which are clinically expressed as episodes of diarrhea and facial flushing (carcinoid syndrome) or Cushing's syndrome . We present the case of a patient with recurrent ACTH-producing MTC.

A synchronous medullary and papillary thyroid carcinoma

<p>The synchronous occurrence of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) is rare (<1%). The medullary component determines the prognosis. A 31-year-old female with no relevant personal or family cancer history presented with swelling on the right side of the neck. A fine-needle aspiration biopsy was positive for MTC and PTC. Mass sequencing of 322 genes associated with cancer came back negative. The histopathological examination revealed synchronous MTC and PTC with thymic and bilateral lymph node metastasis. The patient underwent total thyroidectomy with bilateral radical neck dissection (II-V), central dissection, and mediastinal dissection including the thymus. The extent of surgery is determined by MTC and the analysis of RET and BRAF mutations. Post-operative treatment must include monitoring for specific markers (calcitonin and thyroglobulin, respectively, for MTC and PTC). Based on histopathological results and recurrent PTC, TSH suppression and iodine-131 therapy should be considered. Recurrent MTC must be treated with new targeted therapies.</p>

Targeting Amyloids with [18F]AV-45 for Medullary Thyroid Carcinoma Positron Emission Tomography/Computed Tomography Imaging: A Pilot Clinical Study.

Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine tumor with a high recurrence rate. Amyloid plaques formed from the misfolding of calcitonin are the key characteristics of MTC. Herein, we conducted a first-in-human pilot clinical study by applying a β-amyloid-specific radiotracer, [18F]AV-45, to positron emission tomography (PET)/computed tomography (CT) imaging of MTC. The presence of amyloid plaques in the tumor tissue sections from five MTC patients was confirmed by hematoxylin and eosin (H&E) and Congo Red staining. [18F]AV-45 selectively accumulated in the amyloid plaques in the continued tumor tissue sections with similar distribution patterns to the H&E and Congo Red staining. In addition, the [18F]AV-45 uptake can be largely blocked by its nonradioactive reference compound. The [18F]AV-45 accumulation in the thyroid, neck lymph nodes, and muscles in healthy human subjects is close to the background indicated by PET/CT imaging. In the comparison PET/CT imaging study of a recurrent MTC patient, 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) showed an elevated uptake by multiple neck lymph nodes. In contrast, only one of these neck lymph nodes had increased [18F]AV-45 uptake. Postoperative histopathological analysis confirmed the [18F]AV-45 PET-positive lymph node as MTC with amyloid deposition, while other [18F]FDG positive lymph nodes were free from MTC and amyloid plaques. Thus, [18F]AV-45 showed the promise for the clinical PET/CT imaging of MTC.

Breast metastasis from medullary thyroid carcinoma: a report of a case

BackgroundMetastasis to the breast is rare. We herein report a patient with metastatic medullary thyroid carcinoma to the breast for whom measuring the calcitonin level was an important clue to the correct diagnosis.Case presentationA 54-year-old woman visited our hospital for the treatment of recurrent metastatic medullary thyroid carcinoma due to multiple endocrine neoplasia 2A and breast cancer. Positron emission tomography performed before the operation for metastatic medullary thyroid carcinoma recurrence in the neck showed the accumulation of 18F-fluorodeoxyglucose in the bilateral breast at sites other than the disease in the neck. Ultrasonography revealed multiple tumors in both breasts. A core needle biopsy of three breast tumors was performed. Microscopically, the tumor cells showed solid growth and did not show a tubular structure. She was diagnosed with triple-negative invasive ductal carcinoma. Post-operative positron emission tomography was performed as the serum calcitonin level increased after the operation. The accumulation of 18F-fluorodeoxyglucose in the bilateral breast tumors and lymph nodes in the neck was noted. The possibility of the breast tumors being metastasis of metastatic medullary thyroid carcinoma was considered. Needle aspiration was performed for three breast tumors. The calcitonin level of the washout fluid was measured and found to be ≥ 17,500 pg/mL. Immunohistochemistry showed that the tumor cells were calcitonin-positive and gross cystic disease fluid protein-15-negative. Vandetanib was started as recurrent metastatic medullary thyroid carcinoma with breast metastasis was finally diagnosed. The serum calcitonin level decreased after 1 month.ConclusionAlthough breast metastasis of medullary thyroid carcinoma is rare, a correct diagnosis is indispensable for appropriate treatment. When a breast tumor shows atypical morphological features for breast cancer according to the histopathology in a patient with a history of cancer, metastasis to the breast should be considered. Calcitonin measurement of the needle washout fluid was useful for confirming metastatic medullary thyroid carcinoma.

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: < 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: < 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.

Management of medullary thyroid carcinoma

: Medullary thyroid carcinoma (MTC) is a rare malignancy arising from parafollicular C-cells and accounts for 3–10% of all thyroid malignancies. MTC occurs mostly as a sporadic disease, but in at least 30% of cases is hereditary, caused by RET germline mutations. In this setting, different germline RET mutations lead to distinct clinical phenotypes of hereditary MTC such as familial MTC and multiple endocrine neoplasia 2A and 2B. RET genetic screening should be performed in all new discovered cases of MTC since about 4–10% of patients with apparently sporadic MTC have RET germline mutations and therefore an inheritable disease. Calcitonin (CT) is the most reliable marker of MTC for both diagnosis and follow-up after thyroidectomy. In sporadic MTC, a routine determination of CT in patients with nodular goiter has been correlated to a lower rate of advanced tumor stages. Surgery is the only curative treatment. Since the relatively high risk of multifocal and bilateral disease and the early spread to cervical lymph nodes, total thyroidectomy and central neck lymph node dissection is the standard initial treatment. Lateral neck lymph node dissection might be considered according to imaging results and CT levels. The potential benefit of neck reiterative surgery for persistent or recurrent MTC should be balanced against the increased surgical morbidity in a scarred operative field. The treatment of locally advanced MTC that is not amenable to surgery or metastatic MTC benefits of tyrosine kinase inhibitors that have shown some effects on disease progression. External radiotherapy and cytotoxic chemotherapy have demonstrated little benefit. Prognosis strictly depends on stage of disease at diagnosis, with lower survival and cure rate for stage IV disease. The purpose of this review is to describe the management and treatment of patients with MTC, focusing on biochemical and imaging diagnostic tools, preoperative work-up, treatment and prophylactic surgery for hereditary variants.

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.

Coexistence of medullary thyroid carcinoma and recurrent non-functional pituitary adenoma: a case report

BackgroundMedullary thyroid carcinoma and pituitary adenoma are neuroendocrine tumors and their coexistence has not been reported in the literature, previously. Medullary thyroid carcinoma is a neoplasm of the thyroid gland arising from parafollicular c-cells producing calcitonin, and pituitary adenoma is a benign hyperplasia of the cells of the pituitary gland. Coexistence of these neoplasms can be explained by being affected by simultaneous primary neoplasms or tumor-to-tumor metastasis phenomenon.Case presentationWe present the case of a 60-year-old Persian man who presented to the clinic with a chief complaint of headache for the last 2 months. His past medical history was significant for non-functional pituitary macroadenoma and medullary thyroid carcinoma and he had received a total thyroidectomy and a transsphenoidal surgery several years ago. Diagnostic evaluations revealed that the pituitary adenoma has recurred. He was well and symptom-free after the second transsphenoidal surgery for resection of the adenoma. Noticeably, investigations were negative for any form of multiple endocrine neoplasia syndromes; however, we could not rule them out definitively.ConclusionsTo the best of our knowledge, it is the first case reported in the literature of a patient who has been affected by recurrent non-functional pituitary adenoma and medullary thyroid carcinoma, concomitantly. Although this association can be accidental, it emphasizes the fact that patients with a history of a neoplasm should be monitored regularly in order to diagnose and treat possible second primary cancers in a timely manner. Of note, this consideration is of great importance in patients whose first neoplasms have better prognosis and survival rates, which provide them more time to develop second primary cancers, for example, pituitary adenoma.

Uso della procalcitonina come marker del carcinoma midollare tiroideo

Here we reviewed the literature on the use of procalcitonin (PCT), a precursor of calcitonin (CT), as diagnostic marker of medullary thyroid carcinoma (MTC) in both preoperative and postsurgical setting. To date, about forty articles have been published on this topic. Some of these evaluated the reliability of PCT to detect MTC in thyroid nodule patients, and the other ones investigated the performance of PCT to identify recurrent MTC during postoperative follow-up. Based on published data, PCT measurement appears a promising and reliable serum marker for the diagnosis of MTC. The sample handling of PCT is less laborious and in specific conditions its assay could have significant impact and higher accuracy than CT. Some potential cut-offs have been reported but it would be worthwhile to establish a fixed threshold to use PCT during clinical practice.

Procalcitonin as Marker of Recurrent Medullary Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

BackgroundCalcitonin measurement is pivotal in the management of medullary thyroid carcinoma (MTC), but several pitfalls can affect its reliability. Other potential markers have been proposed, and procalcitonin (ProCT) has been reported as promising. The present study was undertaken to summarize the published data and provide more robust estimates on the reliability of ProCT as marker in the management of patients with MTC.MethodsThe systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The sources comprised studies published through May 2018. Original articles that reported series of MTC patients undergone ProCT during postoperative follow-up were searched. A random-effects model was used for statistical pooling of the data. The I2 index was used to quantify the consistency among the studies. The Egger test evaluated the possible presence of significant publication bias. Quality assessment of the studies was performed according to Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2).ResultsAccording to inclusion and exclusion criteria five papers, reporting 296 MTC patients undergone ProCT evaluation, were finally selected. The number of MTC with recurrence was 140. The pooled sensitivity of ProCT in detecting recurrence was 96% (95% confidence interval [CI], 92% to 99%), with neither heterogeneity (I2=0%) nor publication bias (Egger test, 3.16; P=0.99). The pooled specificity was 96% (95% CI, 87% to 100%) with mild heterogeneity (I2=66.6%), while Egger test was not calculable.ConclusionThe present meta-analysis provides evidence that ProCT is reliable to manage MTC patients during their postoperative follow-up.

Detection rate of somatostatin receptor PET in patients with recurrent medullary thyroid carcinoma: a systematic review and a meta-analysis.

Several articles have demonstrated the high diagnostic performance of somatostatin receptor positron emission tomography (PET) in patients with neuroendocrine tumours (NETs). On the other hand, only a few studies have evaluated the detection rate (DR) of this imaging method in recurrent medullary thyroid carcinoma (MTC). We aimed to perform a systematic review and a meta-analysis of the DR of somatostatin receptor PET or PET/CT in patients with recurrent MTC to add evidence-based data to this setting. A comprehensive computer literature search of studies published in PubMed/MEDLINE and the Cochrane Library Database through May 2017 and regarding somatostatin receptor PET or PET/CT in patients with recurrent MTC was carried out. DR was determined on a per patient-basis. A sub-analysis considering serum calcitonin (Ctn) values was also performed. Nine studies on the diagnostic performance of somatostatin receptor PET or PET/CT in detecting recurrent MTC were discussed in the systematic review. The meta-analysis of these selected studies provided the following DR on a per patient-based analysis: 63.5% [95% confidence interval (95%CI): 49-77]. Heterogeneity among the selected studies was found. DR of somatostatin receptor PET or PET/CT increased in patients with higher serum Ctn levels (83% for Ctn >500 ng/L). In patients with recurrent MTC, somatostatin receptor PET or PET/CT demonstrated a non-optimal DR which increased in patients with higher serum Ctn values. The diagnostic performance of somatostatin receptor PET or PET/CT in recurrent MTC is lower compared to that of the same imaging method in the majority of NETs.

Predictive and prognostic value of 18F-DOPA PET/CT in patients affected by recurrent medullary carcinoma of the thyroid.

Medullary thyroid carcinoma (MTC) is a malignancy accounting for about 5-8% of thyroid cancers. Serum calcitonin and carcinoembryonic antigen (CEA) levels are widely used to monitor disease progression. However, prognostic factors able to predict outcomes are highly desirable. We, therefore, aimed to assess the prognostic role of 18F-DOPA PET/CT in patients with recurrent MTC. 60 patients (mean age 64 ± 13years, range 44-82) with recurrent MTC were eligible from a multicenter database. All patients underwent a restaging 18F-DOPA PET/CT, performed at least 6months after surgery. CEA/calcitonin levels, local recurrences, nodal involvement and metastases at PET/CT were recorded. SUVmax, SUVmean (also normalized to mediastinal uptake) and metabolic tumor volume were automatically calculated for each lesion, by placing a volume of interest around the lesion with 40% of peak activity as threshold for the automatic contouring. The patients were clinically and radiologically followed up for 21 ± 11months. Rate of progression-free survival (PFS), disease-specific survival (DSS) and incremental prognostic value of 18F-DOPA PET/CT over conventional imaging modalities were assessed by Kaplan-Meier curves and Log-Rank test. Cox regression univariate and multivariate analyses were performed for assessing predictors of prognosis. 18F-DOPA PET/CT showed abnormal findings in 27 patients (45%) and resulted unremarkable in 33 (55%). PFS was significantly longer in patients with an unremarkable PET/CT scan (p = 0.018). Similarly, an unremarkable PET/CT study was associated with a significantly longer DSS (p = 0.04). 18F-DOPA PET/CT added prognostic value over other imaging modalities both for PFS and for DSS (p < 0.001 and p = 0.012, respectively). Neither semiquantitative PET parameters nor clinical or laboratory data were predictive of a worse PFS and DSS in patients with recurrent MTC. 18F-DOPA PET/CT scan has an important prognostic value in predicting disease progression and mortality rate.

Diagnostic utility of PET/CT with 18F-DOPA and 18F-FDG in persistent or recurrent medullary thyroid carcinoma: the importance of calcitonin and carcinoembryonic antigen cutoff.

This study sought to evaluate and compare the utility of 18-F-fluorodihydroxyphenylalanine (18F-DOPA) and 18-F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for identification of lesions in patients with recurrent medullary thyroid carcinoma (MTC). In addition, we analyzed the correlation between the calcitonin (Ct), carcinoembryonic antigen (CEA) levels, each doubling time (DT), and PET positivity. We evaluated the reliability of the 150 pg/mL Ct cutoff set by the American Thyroid Association guidelines for further imaging (including 18F-DOPA PET/CT). We prospectively recruited 18 patients with recurrent MTC, identified by elevation of Ct or CEA. Each patient underwent a 18F-FDG PET/CT and a 18F-DOPA PET/CT. Abnormal uptakes were detected with 18F-DOPA (n=12) and 18F-FDG (n=9), (sensitivity of 66.7% vs. 50%; p<0.01). Twenty-eight lesions were detected with 18F-DOPA vs. 16 lesions with 18F-FDG (1.56±1.5 vs. 0.89±1.18 lesions per patient; p=0.01). None of our patients showed additional lesions with 18F-FDG in comparison to 18F-DOPA. Patient-based detection rate increased significantly with Ct levels ≥150 pg/mL vs. Ct<150 pg/mL for both 18F-DOPA (sensitivity 90.9% vs. 28.6%; p=0.013) and 18F-FDG PET/CT (sensitivity 72.7% vs. 14.3%; p=0.025). Using a CEA cutoff of ≥5 ng/mL, detection rates of 18F-DOPA and 18F-FDG PET/CT were 81.1% and 72.7%, respectively. No correlation between Ct-DT or CEA-DT and PET positivity was found. Histological confirmation was obtained in eight patients. 18F-DOPA PET/CT appears to be superior to 18F-FDG PET/CT in detecting and locating lesions in patients with recurrent MTC. This technique tends to be especially useful in patients with negative results in other imaging modalities and Ct≥150 pg/mL or CEA≥5 ng/mL.

68Ga-DOTATATE PET/CT in recurrent medullary thyroid carcinoma: a lesion-by-lesion comparison with 111In-octreotide SPECT/CT and conventional imaging

The aim of this study was to prospectively compare the detection rate of 68Ga-DOTATATE PET-CT with 111In-octreotide SPECT-CT and conventional imaging (CI) in medullary thyroid carcinoma (MTC) patients with increased calcitonin (Ctn) levels but negative CI after thyroidectomy. Fifteen patients with raised Ctn levels and/or CI evidence of recurrence underwent 68Ga-DOTATATE PET-CT, 111In-octreotide SPECT-CT and CI. Histopathology, CI and biochemical/clinical/imaging follow-up were used as the reference standard. PET/CT, SPECT/CT and CI were compared in a lesion-based and organ-based analysis. PET/CT evidenced recurrence in 14 of 15 patients. There were 13 true positive (TP), 1 true negative (TN), 1 false positive (FP) and no false negative (FN) cases, resulting in a sensitivity and accuracy of 100% and 93%. SPECT/CT was positive in 6 of 15 cases. There were 6 TP, 2 TN, 7 FN and no FP cases, resulting in a sensitivity of 46% and accuracy of 53%. CI procedures detected tumor lesions in 14 of 15 patients. There were 13 TP, 1TN, 1 FP and no FN cases with a sensitivity of 100% and accuracy of 93%. A significantly higher number of lesions was detected by PET/CT (112 lesions, p=0.005) and CI (109 lesions, p=0.005) in comparison to SPECT/CT (16 lesions). There was no significant difference between PET/CT and CI for the total number of detected lesions (p=0.734). PET/CT detected more lesions than SPECT/CT regardless of the organ. PET/CT detected more bone lesions but missed some neck nodal metastases evidenced by CI. The number of lesions per region demonstrated by PET/CT and CI were similar in the other sites. 68Ga-DOTATATE PET/CT is superior to 111In-octreotide SPECT/CT for the detection of recurrent MTC demonstrating a significantly higher number of lesions. 68Ga-DOTATATE PET/CT showed a superior detection rate compared to CI in demonstrating bone metastases.

Novel acquisitions in the diagnosis of medullary thyroid carcinoma.

The correct identification of medullary thyroid carcinoma (MTC) has been a challenge since its first description. In the last few years, some advances in this context have been achieved. Here we aimed to review and discuss published data on the more recent acquisition in the diagnosis of MTC. A literature search of the medical databases was conducted by searching papers reporting tool for diagnosis of MTC published in the last years. The search was updated until July 2016. The literature search revealed several relevant articles which focused on different topics of the diagnosis of MTC. The results are reported by four paragraphs, such as 1) fine-needle aspiration; 2) molecular analysis; 3) serum markers; 4) imaging. The measurement of calcitonin in FNA washout fluids is essential due to poor accuracy of conventional cytology to detect MTC. Genetic analysis can help to identify those advanced MTC with poorer prognosis who do not respond to chemotherapy. Procalcitonin may in the next future replace calcitonin as serum diagnostic marker of MTC. Recent evidence based data seem to suggest the emerging role of functional imaging in recurrent MTC in patients with calcitonin serum levels >150 pg/mL.

Postoperative Complications After Prophylactic Thyroidectomy for Very Young Patients With Multiple Endocrine Neoplasia Type 2

The aim of this study was to investigate whether younger age at surgery is associated with the increased incidence of postoperative complications after prophylactic thyroidectomy in pediatric patients with multiple endocrine neoplasia (MEN) 2.The shift toward earlier thyroidectomy has resulted in significantly less medullary thyroid carcinoma (MTC)-related morbidity and mortality. However, very young pediatric patients might have a higher morbidity rate compared with older patients. Hardly any literature exists on complications in the very young.A retrospective single-center analysis was performed on the outcomes of MEN2 patients undergoing a prophylactic total thyroidectomy at the age of 17 or younger. Forty-one MEN2A and 3 MEN2B patients with thyroidectomy after January 1993 and at least 6 months of follow-up were included, subdivided in 9 patients younger than 3 years, 15 patients 3 to 6 years, and 20 patients older than 6 years. Postoperative hypocalcemia and other complications were registered.Twelve (27%) patients developed transient hypocalcemia and 9 (20%) patients suffered from permanent hypocalcemia, with a nonsignificant trend toward higher incidence with decreasing age. Three (7%) patients had other complications, of whom 2 were younger than 3 years.For patients younger than 3 years, the average length of stay (LOS) was 6.7 days, versus 1.7 and 3.5 days, respectively, for the older patient groups (P < 0.05). Patients with complications had a longer LOS compared with patients without (5.0 vs 2.0, P < 0.01).None of the patients had clinical signs of recurrent MTC after a mean follow-up of 10.5 years.Prophylactic thyroidectomy in very young children is associated with a higher rate of complications, causing a significant increased LOS. Irrespective age of surgery, MTC did not recur in any patient. In planning optimal timing of surgery, clinicians should take the risk of complications into account. We advise not to perform total thyroidectomy before the age of 3 for patients defined high risk by the American Thyroid Association guideline.

Long-Term Follow-up in Medullary Thyroid Carcinoma.

After surgery, patients with medullary thyroid carcinoma (MTC) should be assessed regarding the presence of residual disease, the localization of metastases, and the identification of progressive disease. Postoperatively, patients with MTC are staged to separate those at low risk from those at high risk of recurrence. The TNM staging system is based on tumor size, extra-thyroidal invasion, nodal metastasis, and distant spread of cancer. In addition, the number of lymph-node metastases, the number of compartments involved, and the postoperative calcitonin (CTN) and carcinoembryonic antigen (CEA) levels should be documented. The postoperative normalization of the serum CTN level is associated with a favorable outcome. When patients have basal serum CTN levels less than 150pg/ml after a thyroidectomy, any persistent or recurrent disease is nearly always confined to lymph nodes in the neck. When the postoperative serum CTN level exceeds 150pg/ml, patients should be evaluated with imaging procedures, including computed tomography (CT) of the neck and chest, contrast-enhanced magnetic resonance imaging (MRI) and ultrasound (US) of the liver, bone scintigraphy, MRI of the bone, and positron emission tomography (PET)/CT. One can estimate the growth rate of MTC metastases by quantifying increases in tumor size over time from sequential imaging studies analyzed with response evaluation criteria in solid tumors (RECIST), and by determining the tumor marker doubling time from sequential measures of serum CTN or CEA levels over multiple time points. One of the main challenges remains to find effective adjuvant and palliative options for patients with metastatic disease. Patients with persistent or recurrent MTC localized to the neck following thyroidectomy are candidates for neck operations, depending on the tumor extension. Once metastases appear, the clinician must decide which patients require therapy. This requires a balance between the (often) slow rate of tumor progression, which is associated with a good quality of life, and the limited efficacy and potential toxicities of local and systemic therapies. Considering that metastatic MTC is incurable, the management goals are to provide loco-regional disease control, palliate symptoms of hormonal excess, such as diarrhea, palliate symptomatic metastases, like pain or bone fracture, and control metastases that threaten life, such as bronchial obstruction or spinal cord compression. This can be achieved with palliative surgery, external beam radiation therapy (EBRT), or systemic therapy with tyrosine kinase inhibitor (TKI).

Editorial Review of 2014

Editorial Review of 2014

Update on the Cytologic and Molecular Features of Medullary Thyroid Carcinoma

Medullary thyroid carcinoma (MTC) accounts for only 5% to 10% of all thyroid carcinomas, but it is the most aggressive form of well-differentiated thyroid carcinoma, being responsible for 8% to 15% of all thyroid cancer-related deaths. MTC is frequently diagnosed at a locally advanced or metastatic stage, and 10-year survival rates in these cases are <20%. Fine-needle aspiration biopsy of the thyroid gland is an accurate method to diagnose MTC, having a high sensitivity and specificity. The cytologic features of MTC are characteristic and the cytologic diagnosis of classic MTC is often straightforward, especially when combined with immunocytochemistry. However, because of its morphologic heterogeneity and overlap with other tumors, the differential diagnosis of MTC on cytology and on histology is broad with several potential pitfalls. Significant advances have been made over the last decade in understanding MTC. This concerns mainly the early detection of MTC, especially in familial forms (eg, multiple endocrine neoplasia type 2), and the identification of key molecular pathways and alterations which now offer promising targets for specific therapies in progressive MTC cases. Genetic testing (eg, RET mutation) has allowed for early detection in asymptomatic carriers and high-risk patients, with prophylactic thyroidectomy often being curative. Targeted therapies with multityrosine-kinase inhibitors (eg, vandetanib or cabozantinib) have emerged as promising new treatments for recurrent or metastatic MTC. In this review article, we discuss the cytologic features of MTC and its variants, its differential diagnosis, the role of ancillary studies, and the salient molecular features of MTC.