Diagnosis Of Medullary Thyroid Cancer Research Articles

Circulating Tumour Cells and MicroRNA in Thyroid Cancer - a Systematic Review

Background: Thyroid cancer (TC) is the most common endocrine malignancy worldwide. Currently available circulating biomarkers such as thyroglobulin and calcitonin present severe limitations to the diagnosis and management of often difficult-to-diagnose lesions. There is increasing interest in the utility of circulating tumour cells (CTCs) and microRNAs to diagnose and optimise the management of patients with TC.Methods: In this study, we undertake a systematic review to gain a better understanding of the utility of CTCs and microRNAs in the diagnosis and management of patients with TC. A systematic review of the literature was performed by searching electronic bibliographic databases MEDLINE, EMBASE, SCOPUS and Web of Science. Studies which measured CTCs or microRNA levels in peripheral blood from TC patients were included. Review articles, conference abstracts, and foreign language papers were excluded.Results: There were 238 records screened for inclusion. Full texts of 47 articles were reviewed and included for qualitative analysis.CTCs demonstrated value in disease monitoring by distinguishing between disease recurrence and remission in patients with papillary thyroid cancer (PTC) and differentiated thyroid cancer (DTC). Higher CTC counts were associated with poorer progression free survival. This is consistent with CTC studies in other cancers such as breast and colorectal.A total of 31 microRNA biomarker candidates were investigated in studies reviewed. Circulating miR-222, miR-221 and miR-146b were most commonly increased in patients with PTC compared to benign nodules and healthy controls, and were associated with poorer prognostic factors including extrathyroidal invasion and metastatic lymph nodes. Circulating miR-222-3p and miR-17-5p demonstrated discriminatory power between medullary thyroid cancer (MTC) and benign nodules and healthy controls.Conclusion: CTCs demonstrate a promising avenue for disease monitoring and detection of local and distant recurrence in patients with DTC. Several microRNA candidates demonstrate value in diagnosis of PTC and MTC. There is a large degree of heterogeneity in studies assessing theutility of microRNA biomarker candidates. Further studies are warranted to ascertain the value of circulating microRNA in disease monitoring and prognosis.

Occurrence of sporadic medullary thyroid carcinoma in Graves’ disease in association with a RET proto-oncogene mutation

ABSTRACT Background Graves’ disease may be associated with thyroid cancer, particularly differentiated thyroid cancer. Medullary thyroid cancer (MTC) is less common. The occurrence of sporadic MTC in Graves’ disease in the presence of a RET proto-oncogene has never been reported. Clinical presentation A 63-year-old woman was referred for Graves’ disease. A thyroid ultrasound disclosed five nodules, one of which was classified as Eu-Tirads 5 with a size of 6.7 × 6.5× 11 mm. Fine needle aspiration was reported as Bethesda class IV follicular neoplasm of a Hürthle cell subtype. Calcitonin level was found to be elevated. A total thyroidectomy confirmed the diagnosis of MTC and a bilateral cervical lymphadenectomy was performed, with four lymph nodes being infiltrated by MTC. Genetic testing revealed a M918T mutation in the RET proto-oncogene. Conclusion MTC may occur in Graves’ disease, especially if a nodule is present. In this case, genetic testing should always be performed even if MTC is sporadic. Increased incidence of thyroid cancer in autoimmune thyroid diseases, as well as the link existing between autoimmunity, inflammation and carcinogenesis, leads us to hypothesize that the association here reported is not coincidental.

Medullary thyroid cancer: molecular factors, management and treatment.

Medullary thyroid cancer (MTC) is an infrequent neuroendocrine tumor, which amounts to 3–5% of all thyroid malignancies. Approximately 75–80% of MTCs are sporadic neoplasms. The rest of 20–25% are familial cases that belong to multiple endocrine neoplasia (MEN) syndromes, specifically MEN2 and MEN3. These cases of familial MTC are attributed to an activating germline mutation of a tyrosine kinase receptor gene, the rearranged during transfection (RET) proto-oncogene, located on chromosome 10q11.21. These mutations are also found in some cases of sporadic MTC. This review sets forth in summary the accepted guidelines and approaches regarding diagnosis, management, and treatment of MTC. Surgical resection is the standard care, and an early, prophylactic intervention is performed in genetic cases. Further investigation and understanding of the molecular pathways involved in the growth and advancement of MTC is required in order to provide efficient therapy in cases of progressive disease.

Basal and stimulated calcitonin for the diagnosis of medullary thyroid cancer: updated thresholds and safety assessment

Basal and stimulated calcitonin for the diagnosis of medullary thyroid cancer: updated thresholds and safety assessment

Is there a place for measuring serum calcitonin prior to thyroidectomy in patients with a non-diagnostic thyroid nodule biopsy?

To verify the cytopathological Bethesda System classification of thyroid nodule fine-needle aspiration biopsy (FNAB) in MTC patients and to assess the role of preoperative serum calcitonin (CT) levels in the investigation of this neoplasm in medullary thyroid cancer (MTC) patients under observation at the Uopeccan (União Oeste Paranaense de Estudos e Combate ao Câncer). This is a cross-sectional review of medical records of patients monitored at the thyroid cancer outpatient clinic of Uopeccan. Clinical and demographic data, laboratory tests, ultrasound images, and cytopathological findings of MTC patients were evaluated. Among the 360 patients with thyroid cancer monitored in the outpatient clinic, 5.2% (n: 19/360) had MTC. The hereditary form was more prevalent (63.2%), and there was no sex preference. The most common ultrasound findings were hypoechogenicity, solid appearance and microcalcifications. The FNAB diagnoses showed a sensitivity of 47.1%, and the most common cytopathological report was Bethesda category III. Serum CT levels showed good sensitivity (84.6%) for the diagnosis of MTC, and sensitivity levels were directly associated with the size of the nodule and distant metastases. Bethesda category III was more prevalent in this group of MTC patients. Serum CT levels were more sensitive than cytopathology for diagnosis of this neoplasm and were able to identify all patients who could not be diagnosed by FNAB.

Basal and pentagastrin-stimulated calcitonin cut-off values in diagnosis of preoperative medullary thyroid cancer

Background/aimMedullary thyroid cancer (MTC) originates from parafollicular cells (C cell) and produces calcitonin (CT). Basal serum CT was used in the diagnosis and treatment of MTC. If basal CT level is 100 pg/mL or higher, it is likely to have MTC, but if basal CT level is below 10 pg/mL, the probability of developing thyroid disease is low. In cases with basal CT level between 10–100 pg/mL, pentagastrin-stimulated (PS) CT level is studied to evaluate MTC and C cell hyperplasia (CHH). This study aimed to determine cut-off value for basal and PS peak CT level for diagnosis of MTC. Materials and methodsWe retrospectively reviewed files of patients presented to endocrine outpatient clinic of Ege University, Medicine School, between 2010 and 2019; 176 patients with basal CT level of 10–100 pg/mL and patients with PS test were included to the study. ResultsThe receiver operating characteristic curve (ROC) analysis was used to determine cut-off value for basal CT that can discriminate cases with MTC and those with nodular goiter. Cut-off value for basal CT was calculated as 46.5 pg/mL (specificity; 100 %, sensitivity; 74 %). In the ROC analysis for peak PS CT, cut-off value was calculated as 285 pg/mL (specificity:100 %; sensitivity:82 %). When peak CT level was > 290 pg/mL in PS test, both specificity and sensitivity for MTC were determined as 100 %. The PS peak CT level > 285 pg/mL was significant for MTC diagnosis while range of 117–274 pg/mL was significant for CHH. ConclusionIn this study, cut-off value was calculated as 46.5 pg/mL for basal CT, whereas 285 pg/mL for PS peak CT in the diagnosis of preoperative MTC.

ENDOCRINE TUMOURS: Calcitonin in thyroid and extra-thyroid neuroendocrine neoplasms: the two-faced Janus.

An increased calcitonin serum level is suggestive of a medullary thyroid cancer (MTC), but is not pathognomonic. The possibility of false positives or other calcitonin-secreting neuroendocrine neoplasms (NENs) should be considered. Serum calcitonin levels are generally assessed by immunoradiometric and chemiluminescent assays with high sensitivity and specificity; however, slightly moderately elevated levels could be attributable to various confounding factors. Calcitonin values >100 pg/mL are strongly suspicious of malignancy, whereas in patients with moderately elevated values (10-100 pg/mL) a stimulation test may be applied to improve diagnostic accuracy. Although the standard protocol and the best gender-specific cut-offs for calcium-stimulated calcitonin are still controversial, the fold of the calcitonin increase after stimulation seems to be more reliable. Patients with MTC show stimulated calcitonin values at least three to four times higher than the basal values, whereas calcitonin-secreting NENs can be distinguished from a C-cell disease by the absence of or <two-fold response to stimulation. The measurement of calcitonin in fine-needle aspirate washout (FNA-CT) and calcitonin immunocytochemical staining from thyroid nodules are ancillary methods that may significantly improve MTC diagnosis. The present review examines the gray areas in the interpretation of calcitonin measurement in order to provide a tool to clarify the origin of calcitonin secretion and differentiate the behavior of the two-faced Janus of neuroendocrinology: intra-thyroid (MTC) and extra-th9yroid NENs.

Calcitonin Levels in Thyroid Disease Are Not Affected by Autoimmune Thyroiditis or Differentiated Thyroid Carcinoma

Introduction: Association between hypercalcitoninemia and pathological conditions such as autoimmune thyroiditis (AIT) or differentiated thyroid carcinoma (DTC) has been addressed, with conflicting results. We evaluated the prevalence and the clinical relevance of elevated basal serum calcitonin (CT) levels in non-neoplastic (nodular goiter [NG] and AIT) and neoplastic thyroid diseases (DTC). Methods: We retrospectively evaluated 3,250 consecutive patients with thyroid nodular disease who underwent fine-needle aspiration cytology with adequate sample. After exclusion of medullary thyroid cancer (MTC) patients were divided according to the presence/absence of thyroid autoimmunity into NG or nodular autoimmune thyroiditis (N-AIT) and, according to cytological results, in benign or suspicious/malignant nodules. Results: One hundred ninety-seven/3,250 patients (6.0%) showed CT level >10 pg/mL. In 11/3,250 (0.3%) cases, a final histological diagnosis of MTC was made, while the remaining 186/3,250 patients (5.7%) had non-MTC-related hypercalcitoninemia (CT > 10 pg/mL). According to cytological diagnosis, the rate of hypercalcitoninemia was similar in class II and class V–VI groups (5.4 vs. 6.9%, p = 0.4). The occurrence of hypercalcitoninemia was significantly higher in patients with NG (166/2,634 [6.3%]) than in patients with N-AIT (20/605 [3.3%]) (p = 0.004). However, after matching by sex, no difference was found between the 2 groups (NG and N-AIT). These results were confirmed in 598 patients submitted to surgery. Conclusions: AIT and DTC seem not to affect serum CT levels in patients with thyroid nodules. Therefore, hypercalcitoninemia, in these patients, should be submitted to the same diagnostic workup than patients without AIT or DTC.

Medullary Thyroid Cancer Patient’s Assessment of Quality of Life Tools: Results from the QaLM Study

Background: Medullary thyroid cancer (MTC) is a neuroendocrine tumour and a rare variant of thyroid cancer with different aetiology, presentation and treatment to differentiated thyroid cancer. Currently available thyroid cancer-specific quality of life (QoL) tools focus on issues and treatments more relevant to patients with differentiated thyroid cancer and therefore may not address issues specific to a MTC diagnosis and cancer journey. Method: This prospective multicentre randomised study involved 204 MTC patients completing four quality of life questionnaires (QOLQ) and stating their most and least preferred. The questionnaires were a general instrument, the EORTC QLQ-C30, two disease-specific tools, the MD Anderson Symptom Inventory (MDASI) thyroid module and the City of Hope Quality of Life Scale/THYROID (amended) and the neuroendocrine questionnaire, EORTC QLQ-GINET21. Patients were randomised to complete the four questionnaires in one of 24 possible orders and then answered questions about which tool they preferred. The primary outcome measure was patients’ preferred QoL instrument for describing their concerns and for facilitating communication with their healthcare professional. Secondary analyses looked at differences between preferred QOLQs amongst patient subgroups (WHO performance status [0 and 1+], disease stage: early [T1–3, N0 or N1A], metastatic [T4, any T N1b] and advanced [any T any N M1], and type of MTC [sporadic and inherited]), identification of MTC patients’ least preferred questionnaire and clinicians’ views on the QoL tools in terms of their ability to highlight problems not otherwise ascertained by a standard clinical review. Results: No evidence of a difference was observed for most preferred QOLQ (p = 0.650). There was however evidence of a difference in least preferred questionnaire in the cohort of 128 patients who stated their least preferred questionnaire (p = 0.042), with 36% (46/128) of patients choosing the EORTC QLQ-GI.NET21 questionnaire. Subgroup analyses showed that there was no evidence of a difference in patients’ most preferred questionnaire in sporadic MTC patients (p = 0.637), patients with WHO PS 0 or 1+ (p = 0.844 and p = 0.423) nor when comparing patients with early, advanced local or metastatic disease (p = 0.132, p = 0.463 and p = 0.506, respectively). Similarly, subgroup analyses on patients’ least preferred questionnaires showed no evidence of differences in sporadic MTC patients (p = 0.092), patients with WHO PS 0 or 1+ (p = 0.423 and p = 0.276), nor in early or metastatic disease patients (p = 0.682 and p = 0.345, respectively). There was however some evidence to suggest a difference in least preferred questionnaire in patients with advanced local stage disease (p = 0.059), with 43% (16/37) of these patients choosing the EORTC QLQ-GI.NET21 questionnaire. Conclusions: MTC patients regardless of their performance status, disease aetiology and disease burden did not express a preference for any one particular questionnaire suggesting any of the tools studied could be utilized in this patient cohort. The least preferred questionnaire being a gastrointestinal NET specific tool suggests that diarrhoea was not a significant symptom and concern for the population studied.

Early diagnosis of medullary thyroid cancer in case of low serum calcitonin: Role of calcitonin measurement in fine-needle aspiration washout fluid

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Basal and stimulated calcitonin for the diagnosis of medullary thyroid cancer: updated thresholds and safety assessment

PurposeReliable cut-offs for basal (bCT) and calcium stimulated calcitonin (casCT) are needed for an early and accurate diagnosis of medullary thyroid cancer (MTC).Patients and methodsFifty-four new patients with nodular goiter were enrolled and analysed together with those previously published by our group for a total of 135 cases. bCT and casCT were measured by a highly sensitive method and the results compared with histological findings. In a subgroup of patients, cardiac rhythm was recorded before and during the calcium test.ResultsIn both females (F) and males (M), there was a significant correlation between tumor size and bCT levels (P < 0.001). The receiver operating characteristic plot analyses showed that, for bCT, the new cut-off points able to separate non-MTC from MTC patients were > 30 (F) and > 34 pg/mL (M), whereas the best casCT thresholds were > 79 (F) and > 466 pg/mL (M). bCT was shown to harbour a high accuracy, though some cases were diagnosed only upon stimulation test. Importantly, combining bCT, below or above the cut-offs, with casCT above the cut-offs, all the MTC cases were correctly identified. A reversible sinus bradycardia was observed in 9% of cases during the test.ConclusionsRefined cut-offs for bCT and casCT in patients with nodular goiter are reported. Sensitive bCT was shown to have a high accuracy, but the combination with casCT data was needed to identify all MTC cases. The reliability and safety of calcium test strongly favour the routine use of CT determination in nodular thyroid disease.

Cost-effectiveness of routine calcitonin screening and fine-needle aspiration biopsy in preoperative diagnosis of medullary thyroid Cancer in the United States.

examine the cost-effectiveness of routine Calcitonin (Ctn) screening test in the United States. Markov chain model was developed that compares fine-needle aspiration biopsy (FNAB) with Ctn screening vs. FNAB-only in the evaluation of a thyroid nodule with non-highly suspicious findings. Follow-up time was set as 10years. Costs and probabilities values were obtained from literature, and National Cancer Database. Cost data is expressed in U.S$ and effectiveness is expressed in Quality-adjusted-life-year (QALY). Incremental cost-effectiveness ratio (ICER) was calculated comparing both study arms. Routine Ctn screening was cost-effective compared to FNAB-only in all tested categories except when cutoff value of 10pg/ml was applied. Among the tested categories, the application of universal routine Ctn screening with Ctn value>50pg/ml considered a positive test produced the most cost-saving scenario. The final accrued cost at the end of 10years in the FNAB-only arm was $4238.93 with a final effectiveness of 8.717 QALY. While the final cost in the FNAB-with routine Ctn screening was $4345.04 with a final effectiveness of 8.722 QALY. ICER of routine Ctn screening compared to FNAB-only was $23278.61/QALY (<Willing-To-Pay threshold of $50,000/QALY). Based on sensitivity analyses, Ctn testing is cost-effective if the test cost is less than $236.03. Routine Ctn screening is a cost-effective strategy in US if the cost is less than $236.03. Although Ctn screening is not perfect in detecting MTC at early stages, it is a cost-effective alternative of discovering MTC after thyroid lobectomy or on follow-up of a thyroid nodule.

Early Diagnosis of Medullary Thyroid Cancer: Are Calcitonin Stimulation Tests Still Indicated in the Era of Highly Sensitive Calcitonin Immunoassays?

Background: Measurements of both basal (b) calcitonin (CT) and calcium (Ca)-stimulated CT (Ca-sCT) levels are performed to identify medullary thyroid cancer (MTC) at an early stage when used as part of the diagnostic workup of thyroid nodules (CT screening). Novel immunochemiluminometric assays, which are highly sensitive and specific for monomeric CT and avoid cross-reactivity, have been introduced over the past decade. No prospectively generated data have so far become available to answer the frequently raised question as to whether Ca-sCT in contrast to bCT alone is helpful and, therefore, still indicated for the early detection of MTC. Methods: Ca-stimulation tests were performed in 149 consecutive patients with thyroid nodules and elevated bCT. Regardless of Ca-sCT levels, all patients had an operation applying a uniform surgical protocol, including thyroidectomy and systematic lymph node dissection. Recently published sex-specific cutoff levels for the differentiation of MTC and other C-cell pathologies (C-cell hyperplasia [CCH]) were used to compare the diagnostic performance of bCT or Ca-sCT alone and in combination using receiver-operating characteristic (ROC) analysis. In addition, CT cutoff levels to predict lateral lymph node metastasis were evaluated for bCT compared with Ca-sCT. Follow-up for all patients was documented and correlated with initial CT levels. Results: MTC was identified in 76 (50.1%) patients, in 21/76 (27.6%) with lymph node and in 4 (5.3%) with distant metastasis. Using predefined cutoff levels, patients could effectively be subdivided into a group above the cutoff level with definitive diagnosis of MTC (100%) and below (gray zone) with a significant overlap of CCH and MTC (all classified as pT1a; males: 19/58 [37.5%], females: 7/41 [17.1%]). The areas under the ROC curve (AUC) were excellent for the diagnosis of MTC in all tests. Determination of bCT proved to be superior for both diagnosing MTC in males (AUC for bCT: 0.894; AUC for Ca-sCT: 0.849) and females (bCT: 0.935; Ca-sCT: 0.868) and also for diagnosing lymph node metastasis in the lateral compartment (males: bCT: 0.925; Ca-sCT: 0.810; females: bCT: 0.797; Ca-sCT: 0.674). Combining both tests did not improve diagnostic accuracy. Using a cutoff level of >85 pg/mL for females and >100 pg/mL for males, the sensitivity for diagnosing lateral neck lymph node metastasis was 100%. Below these cutoff levels, no patient showed persistent or recurrent disease (median follow-up: 46 [ ± 27] months). Conclusions: Predefined sex-specific bCT cutoff levels are helpful for the early detection of MTC and for predicting lateral neck lymph node metastasis. Ca-sCT did not improve preoperative diagnostics. bCT levels >43 and >100 pg/mL for males and of >23 and >85 pg/mL for females are relevant for advising patients and planning the extent of surgery.

Application of Ultrasonography in the Diagnosis of Medullary Thyroid Cancer

Despite its low incidence,medullary thyroid carcinoma(MTC)is featured by its fast progression and poor prognosis.Early diagnosis and treatment is therefore particularly important.As a convenient and non-invasive diagnostic tool,ultrasound plays a key role in the diagnosis and follow-up of MTC.In recent years,the application of conventional ultrasound,ultrasonic elastography,and ultrasound-guided fine needle aspiration biopsy has dramatically improved the diagnostic accuracy of MTC.

PSMA expression level predicts differentiated thyroid cancer aggressiveness and patient outcome

BackgroundProstate-specific membrane antigen (PSMA) is overexpressed on the endothelial cells of tumor neo-vessels of several solid malignancies, including differentiated thyroid cancer (DTC). We aimed to test the potential role of PSMA as a biomarker for DTC aggressiveness and outcome prediction.We retrospectively screened all patients who underwent thyroidectomy between 1 January 2010 and 31 December 2017 in our institution. Applying the inclusion (histological diagnosis of thyroid cancer and tissue availability) and exclusion criteria (no clinical or follow-up data or diagnosis of medullary thyroid cancer), a cohort of 59 patients was selected. The monoclonal mouse anti-human PSMA antibody was used to stain tissue sections. A 3-point scale was used to score PSMA positivity: 0–5% expression was considered as negative (score 0), 6–50% as moderately positive (score 1), and 51–100% as highly positive (score 2). A cumulative score (0–10%, 11–79%, and 80–100%) was also explored. Univariate and multivariate logistic regression analyses were performed to predict the presence of distant metastases, chosen as endpoint of aggressiveness. The area under the curve (AUC) was calculated. Cox models were built to predict patient outcome in terms of recurrence, iodine refractoriness, and status at last follow-up, which were calculated using the Kaplan-Meier failure function.ResultsAt immunostaining, 12, 25, and 22 patients had scores of 0, 1, and 2, respectively. According to the cumulative score, PSMA expression was ≤ 10% in 17 cases, 11–79% in 31 cases, and ≥ 80% in 11 cases. At multivariate analysis, age, sex, histotype, vascular invasion, T and N parameters, and PSMA positivity were significant predictors of distant metastases. The AUC was 0.92. Recurrence or progression occurred in 19/59 patients. Twelve patients developed radioiodine (RAI) refractoriness, after a median time of 17 months (range 2–32). One patient died of DTC; 46 of the 58 patients alive at last follow-up were disease free. Median DFS was 23 months (range 3–82). The final multivariate model to predict RAI refractoriness included as covariates the stage, high PSMA expression (≥ 80%), and the interaction between moderate PSMA expression (11–79%) and stage.ConclusionsPSMA, a marker of neovasculature formation expressed by DTC, contributes in the prediction of tumor aggressiveness and patient outcome.

SUN-598 Neck Pain as an Initial Presentation of Medullary Thyroid Cancer

Background: Neck pain is common in adults and can be caused by various conditions, most commonly due to musculoskeletal disorder. Thyroid cancer is not usually considered as an etiology for neck pain. We report a patient with an initial presentation of neck pain due to medullary thyroid cancer (MTC). Case Presentation: A 40-year-old female without significant medical history initially presented to her primary care provider with 12 months of left-sided neck pain, point tenderness in the lower neck, and minimal improvement in pain despite multiple courses of physical therapy for presumed musculoskeletal pathology. She noted recent hoarseness, but no esophageal, respiratory, or endocrine symptoms. On physical examination, a discrete left-sided thyroid nodule was palpated. Thyroid ultrasound confirmed a 1.0 x 1.0 x 1.5 cm solid, hypoechoic, taller than wide nodule with irregular borders in the left thyroid lobe. Thyroid function tests including TSH and free T4 were normal. Fine needle aspiration (FNA) of the nodule showed numerous malignant appearing cells with background amyloid suggestive of MTC. Serum calcitonin and CEA were found to be elevated to 206 pg/mL and 8.5 ng/mL, respectively (reference ranges 0-5 pg/mL and 0.2-4.7 ng/mL). Calcium stimulation testing was performed with elevation of calcitonin to 413 pg/mL. Further evaluation disclosed left-sided vocal fold paresis. She was scheduled for total thyroidectomy with central and left lateral neck lymph node dissections and referred for genetic testing. Discussion: Neck pain is an uncommon presentation of thyroid cancer with a reported prevalence of 22% in patients with MTC, 6% with papillary thyroid cancer (1), and 26% in anaplastic thyroid cancer (2). Diagnosis of MTC is usually made by FNA and confirmed with elevated serum calcitonin. In indeterminate cases, calcium stimulation testing can be a useful adjunct to confirm MTC. Given its association with familial tumor syndromes, genetic testing is recommended in all new MTC cases to identify at risk families for early intervention, potentially to include prophylactic thyroidectomy. MTC patients also require serial calcitonin monitoring after surgery to identify recurrences and residual disease. It is important to examine the neck and thyroid gland carefully in patients with neck pain.

Clinical utility of genetic diagnosis for sporadic and hereditary medullary thyroid carcinoma

Medullary thyroid cancer (MTC) is a rare thyroid tumor whose prevalence is 3–5% among all thyroid tumors. The pathogenesis of MTC is mainly related to germline or somatic RET activating point mutations that are causative of hereditary and sporadic cases, respectively. Hereditary MTC can occur as multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B) and familial MTC (FMTC) that differ for the association with other endocrine neoplasia. Germline RET point mutations are prevalently localized in exons 5, 8, 10–11, 13–16 and a significant genotype-phenotype correlation has been observed. RET genetic screening is mandatory in all patients with a diagnosis of MTC regardless from their apparent sporadic origin. The identification of RET germline mutation in an apparently sporadic case is of great clinical utility because it allows the identification of those subjects who will develop the tumor. RET positive relatives must undergo clinical and biochemical tests to verify if the MTC is already present and, according to the type of RET mutation, they have to be screened for the presence of pheochromocytoma and/or hyperparathyroidism. If a MTC is already present patients must be surgically treated. If MTC is not yet present subjects will be followed up with basal and stimulated calcitonin serum measurement, which is the serum marker of MTC. Indeed, RET negative subjects can be reassured that they do not run any risk to develop the disease as well as their children. In conclusions RET genetic screening allows the identification of the hereditary/sporadic nature of MTC and of a relevant percentage of hidden familial MTC. Furthermore, it favors the early diagnosis of MTC in RET positive subjects. RET positive patients and no clinical evidence of MTC can be followed and surgical treatment can be delayed. Finally RET negative relatives do not need to be further monitored.

Baseline and stimulated calcitonin: Thresholds for the diagnosis of medullary thyroid cancer

Annales d'Endocrinologie - In Press. Accepted Manuscript Available online since vendredi 12 avril 2019

Small Cell Carcinoma: a Rare Subtype of Thyroid Cancer with Unanticipated Prognosis.

The prognosis of small cell thyroid carcinoma (SCTC) in a large cohort has not been well reported in the literature. In this study, we analyzed the mortality of SCTC, in comparison to medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC), based on the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, to determine the prognosis of SCTC. Information regarding patients with a diagnosis of MTC, ATC, or SCTC, between 2004 and 2013, was acquired from the SEER database. Patient survival curves were assessed by Cox proportional hazards regression analyses, Kaplan-Meier analyses, and log-rank tests. In a Kaplan-Meier analysis of the entire cohort of thyroid cancer patients, cancer-specific survival declined sharply for patients with SCTC, but it declined more modestly for patients with MTC. The cancer-specific survival was not significantly different between SCTC and ATC. Unadjusted Cox regression analysis showed that SCTC had a higher cancer-specific mortality than MTC but a similar prognosis as ATC. SCTC showed a higher cancer-specific mortality than MTC and ATC after adjustments for various confounding factors. SCTC was found to have a more highly lethal clinical course than MTC and had a similar death rate to ATC. Therefore, we recommend that aggressive, radical treatment like surgery or radiation should be performed for these patients.

A novel combined transoral and transcervical surgical approach for recurrent metastatic medullary thyroid cancer to the parapharyngeal space

Medullary thyroid cancer (MTC) represents less than 1% of all thyroid cancers. Complete surgical resection remains the mainstay of treatment for locoregional disease. Unfortunately, patients with recurrence may present with metastasis to challenging anatomic locations. We describe the first case of a recurrent MTC metastatic to the parapharyngeal space (PPS) that was managed using a combined transoral robotic surgery (TORS) and transcervical (TC) approach. We review the presentation, natural history, diagnosis and management of recurrent MTC, and describe a novel combined TORS-TC surgical approach for the treatment of PPS metastasis. A 66-year-old male with history of MTC treated with total thyroidectomy in 2000 and a liver resection in 2011 for metastatic MTC was referred to our Head and Neck Surgery Clinic in October 2016 due to increased calcitonin and CEA levels. Exam was significant for mild right tonsillar/pharyngeal bulging and induration. Imaging with PET-CT and MRI showed an enlarging ovoid mass centered within the right PPS without the presence of another systemic metastasis. FNA was consistent with MTC. The patient was taken to the operating room for a combined TORS-TC approach. Final pathology was consistent with metastatic MTC. Until recently, PPS tumors have been managed using highly morbid and cosmetically disfiguring open surgical approach. TORS provides a safe and effective alternative.