Calcitonin Screening Research Articles

The impact of preoperative calcitonin screening on the prognosis of patients with medullary thyroid cancer: a retrospective multicenter cohort study

The impact of preoperative calcitonin screening on the prognosis of patients with medullary thyroid cancer: a retrospective multicenter cohort study

The impact of preoperative calcitonin screening on the prognosis of patients with medullary thyroid cancer: a retrospective multicenter cohort study.

There is still controversy in different guidelines regarding the necessity of routine preoperative calcitonin (Ctn) testing in medullary thyroid cancer (MTC). The level of preoperative Ctn may influence the extent of surgery. This retrospective multicenter cohort study involved 149 MTC patients from 6 centers between 2013 to 2023. Clinical characteristics, surgical procedure and clinical outcomes were compared between Ctn-screened and Non-screened group. Kaplan-Meier method was used to estimate recurrence-free survival (RFS) and overall survival (OS). In total, 127 MTC patients with preoperative Ctn screening and 22 MTC patients without screening were analyzed. MTC patients with preoperative Ctn screening underwent more radical surgical procedures including total thyroidectomy and lymph node dissection, compared to those without screening (84.3% vs. 68.2% and 91.3% vs. 72.7%, respectively). The rate of recurrence and death were lower in the Ctn-screened group (16.1% vs. 36.4%, 0.8% vs. 18.2%, respectively). The survival curve showed a significantly better overall survival in Ctn-screened group than Non-screened group (HR:17.932, 95% CI 1.888-170.294, p-value = 0.001), while no significant difference was observed of RFS between two groups (HR:1.6, 95% CI 0.645-3.966, p-value = 0.307). Preoperative Ctn screening can prompt surgeons choosing more radical initial surgical treatment for MTC patients, potentially leading to better long-term outcomes. Further evaluation of the cost-effectiveness of routine Ctn screening in thyroid nodule patients is warranted.

30years of prophylactic thyroidectomy for hereditary medullary thyroid cancer : Amilestone in translational medicine

Medullary thyroid cancer (MTC) is the most frequent manifestation of multiple endocrine neoplasia type 2 (MEN2) that determines the oncological outcome. Germline mutations in the rearranged during transfection (RET) protooncogene, atumor suppressor gene on chromosome 10q11.2, were identified 30 years ago as the genetic basis of MEN2 and published in 1993 and 1994. These seminal findings gave rise to the concept of prophylactic thyroidectomy for asymptomatic gene mutation carriers based on apositive RET gene test, which has become the standard of care ever since. Clinical genetic investigations showed genotype-phenotype correlations with respect to the individual gene mutation regarding the penetrance and onset of MTC and to alesser extent also with respect to the other components of MEN2, pheochromocytoma and primary hyperparathyroidism. From this a clinically relevant risk stratification could be derived. Initially, the optimal timing of prophylactic thyroidectomy was primarily based on the RET genotype alone, which was not sufficient for a precise age recommendation and subsequently required additional consideration of calcitonin serum levels for fine tuning. Calcitonin levels first show the risk of lymph node metastasis when they exceed the upper normal limit of the assay independent of carrier age and RET mutation. Routine calcitonin screening of patients with nodular thyroid disease, screening of families on identification of MEN2 index patients, and pre-emptive thyroidectomy in carriers of gene mutations with normal calcitonin levels have led to the fact that nowadays, 30years after the first description of the gene mutations causing the disease, the life-threatening hereditary MTC has become curable: ashining example for the success of translational transnational medical research for the benefit of patients.

Latest Progress in Risk-Adapted Surgery for Medullary Thyroid Cancer.

(1) Background: The wider adoption of a preoperative ultrasound and calcitonin screening complemented by an intraoperative frozen section has increased the number of patients with occult sporadic medullary thyroid cancer (MTC). These advances offer new opportunities to reduce the extent of the initial operations, minimizing operative morbidity and the risk of postoperative thyroxin supplementation without compromising the cure. (2) Methods: This systematic review of the international literature published in the English language provides a comprehensive update on the latest progress made in the risk-adapted surgery for sporadic and hereditary MTC guided by an intraoperative frozen section. (3) Results: The current evidence confirms the viability of a hemithyroidectomy for desmoplasia-negative sporadic MTC. To add an extra safety margin, the hemithyroidectomy may be complemented by a diagnostic ipsilateral central node dissection. Despite the limited extent of the surgery, all the patients with desmoplasia-negative sporadic tumors achieved a biochemical cure with excellent clinical outcomes. A hemithyroidectomy decreases the need for postoperative thyroxine substitution, but a total thyroidectomy may be required for bilateral nodular thyroid disease. Hereditary MTC is a different issue. Because each residual thyroid C cell carries its own risk of malignant progression, a total thyroidectomy remains mandatory for hereditary MTC. (4) Conclusion: In experienced hands, a hemithyroidectomy, which minimizes morbidity without compromising the cure, is an adequate therapy for desmoplasia-negative sporadic MTC.

An old friend, a new insight: Calcitonin measurement in serum and aspiration needle washout fluids significantly increases the early and accurate detection of medullary thyroid cancer.

The sensitivity of cytological (CY) evaluation after fine-needle aspiration (FNA) for detecting medullary thyroid carcinoma (MTC) is a subject of controversy. The routine use of serum calcitonin (CT) in patients with thyroid nodules is not universally adopted. The authors conducted CT screening of FNA washout fluid (FNA-CT) to address the diagnostic challenges. The objective was to assess the contributions of serum CT, FNA cytology (FNA-CY), and FNA-CT to the diagnosis. Between February 2019 and June 2022 (group 1), the authors prospectively screened the CT of patients with thyroid nodules. Both FNA-CY and FNA-CT were performed for patients with persistently elevated CT values. The sensitivity of FNA-CY, serum CT, and FNA-CT for accurate diagnosis was evaluated. Additionally, the authors retrospectively examined data from patients with thyroid nodules before CT screening (2008-2019) (group 2). They compared the characteristics of MTC patients in groups 1 and 2. MTC was identified in 30 patients (0.25%) in group 1 and 19 (0.07%) in group 2. A FNA-CT cutoff value of 4085.5pg/mL detected MTC with a sensitivity of 96.8%, and a serum CT cutoff value of 28.3pg/mL detected MTC with a sensitivity of 86.7%. In contrast, FNA-CY detected MTC with a sensitivity of 42.4%. In group 1, 18 patients (60%) with MTC were diagnosed with microcarcinoma, whereas only two patients (10.5%) in group 2 had microcarcinoma. This study detected MTC earlier by routinely measuring serum CT in all patients with nodular thyroid disease and performing FNA-CT in those with elevated values. FNA-CT and serum CT sensitivities were significantly higher than those of FNA-CY. This study revealed different FNA-CT cutoff values compared to other studies, emphasizing the need for determining clinic-specific cutoff values.

Update on Calcitonin Screening for Medullary Thyroid Carcinoma and the Results of a Retrospective Analysis of 12,984 Patients with Thyroid Nodules.

We provide an update on calcitonin (Ctn) screening for the early detection of medullary thyroid carcinoma (MTC) and present the results of a large single-center analysis evaluating sex-specific cut-off-levels and long-term courses. A total of 12,984 consecutive adult patients (20.1% male and 79.9% female) with thyroid nodules who had undergone routine Ctn measurement were retrospectively analyzed. Patients with confirmed suspicious Ctn values were referred for surgery. Ctn measurements were elevated in 207 (1.6%) patients, with values below twice the sex-specific reference limit in 82% of these cases. Further clarification was possible in 124/207 cases, of which MTC could be ruled out in 108 cases. Histopathological assessment confirmed MTC in 16/12,984 patients. Our extrapolated MTC prevalence of 0.14% is significantly lower than that described in early international screening studies. The stimulation test can usually be dispensable when using a decision-making concept based on sex-specific basal Ctn cut-off values. Ctn screening is recommended even in patients with very small thyroid nodules. High quality standards in pre-analytics, laboratory measurements, and the interpretation of data must be ensured, as well as close interdisciplinary cooperation between medical disciplines.

Diagnosis of Medullary Thyroid Cancer During COVID-19 Pandemic, the Benefit of Using a Standardized Protocol

Introduction: The reported prevalence of malignancy in thyroid nodules ranges from 4% to approximately 10%, with a small percentage (~2-8%) being medullary thyroid cancer (MTC). During the COVID-19 pandemic, elective thyroid FNA was temporarily halted at our institution. In response to this, our institution has devised a new protocol to aid in the detection of MTC, which includes serum calcitonin measurement as a surrogate marker for potential MTC. A severely elevated calcitonin (>100 pg/mL) is considered for surgery even without FNA diagnosis. We present a case of MTC that was detected due to the adopting of this protocol during COVID-19 pandemic at the Phoenix VAMC. Case Presentation: 71 year old male with an incidentally noted 3.0 cm solid, hypoechoic nodule with internal calcification, TI-RADS category 5. TSH level was normal at 3.309 mIU/mL. The patient denied any personal or family history of thyroid cancer, MEN syndrome, radiation exposure, or compressive symptoms. Following established protocol published by our institution in clinical thyroidology we performed a serum calcitonin that came back elevated at 1515 pg/mL (normal < 10 pg/mL). Given the marked elevation in serum calcitonin levels and highly suspicious radiographic appearance of the thyroid nodule, we strongly suspected medullary thyroid cancer and elected to send him directly for total thyroidectomy without performing FNA. The patient underwent total thyroidectomy with central neck dissection. Pathology showed a 3.2 cm medullary thyroid carcinoma without extrathyroidal extension or perineural invasion. Lymphovascular invasion was present. 6/10 central comparement lymph nodes were positive for metastatic disease. Postoperative calcitonin level was 2 pg/mL. Discussion: Our patient had markedly elevated serum calcitonin levels in addition to a high-risk ultrasonographic features, which was highly suspicious for MTC. Per our COVID-19 protocol, we measured the serum calcitonin level to screen for MTC and then referred him directly to surgery without FNA given the high suspicion for MTC. By using this protocol, we were able to diagnose and treat MTC expeditiously. The measurement of serum calcitonin is still controversial in the U.S, with the ATA remaining equivocal on this method. We believe that our case can serve as a practical example that validates our institution’s use of calcitonin screening of thyroid nodules in diagnosing MTC during the COVID-19 pandemic.

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.

Medullary thyroid carcinoma and multiple endocrine neoplasiatype 2

Medullary thyroid carcinoma (MTC) is a rare malignancy and compromises only 3 % of all thyroid carcinomas. MTC cells secret calcitonin, which serves as a sensitive tumor marker for screening and follow-up of MTC. Calcitonin screening in patients with nodular goiter allows for early diagnosis of MTC and surgical curative treatment. In 25 % of patients MTC occurs as an integral part of multiple endocrine neoplasia type 2 (MEN2), an autosomal dominant inherited tumor syndrome. It is caused by germline mutations in the RET protooncogene. In gene carriers early diagnosis and treatment through prophylactic thyroidectomy is possible. MTC is a slowly growing tumor with a good prognosis and 5and 10 year survival rates up to 80 and 60 %. In the follow-up a dynamic risk stratification allows for a personalized disease management. In symptomatic and progressive metastasizing MTC tyrosine kinase inhibitors are an effective therapy.

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.

Cure and survival of sporadic medullary thyroid carcinoma following systematic preoperative calcitonin screening.

The improvement in outcome of sporadic medullary thyroid carcinoma (MTC) during the last decades remains controversial, even if a trend toward a better prognosis has been recently proposed. This study was aimed to determine the time trend cure and survival rates in sporadic MTC according to the use of systematic preoperative calcitonin screening. Retrospective analysis of 178 sporadic MTC patients operated between 1980 and 2017 was performed. The impact of prognostic factors on cure and survival following the introduction of routine preoperative calcitonin screening in 2001 was evaluated according to the year of surgery. Since 2001, a significant decline of node-positive tumors (from 56.1 to 34.7%) and advanced stage at diagnosis (stage III/IV from 56.1 to 34.7%) occurred, with a concomitant significant increase in cure rate (64.5% vs 38.6%; p = 0.0012) and survival (p < 0.05). At univariate analysis, the cure was achieved more frequently in more recently operated patients (64.5% vs 38.6%; p = 0.0012), in disease staging I/II (86.5% vs 13.5%; p < 0.0001), in patients undergoing preoperative calcitonin screening (63.8% vs 23.5%; p < 0.0001) and in the absence of lymph node metastases (86.5% vs 13.5%; p < 0.0001). At multivariate analysis, only preoperative calcitonin screening and stage at diagnosis turned out to be significant independent prognostic factors for cure and survival. The outcome of sporadic MTC improved in the new millennium; diagnosis was achieved earlier, at a less advanced stage. Routine preoperative calcitonin screening may have contributed to improve cure and survival rates.

CALCITONIN REVISITED IN 2020.

Calcitonin (CT) is a polypeptidic hormone specifically secreted by the thyroid parafollicular cells (C cells) and tangentially involved in human phosphocalcic and bone metabolism. CT from other species (e.g. salmon) is more potent than human CT and has limited therapeutic applications. The neoplastic proliferation of C cells leads to medullary thyroid carcinoma (MTC) generally characterized by an increase of CT secretion. Serum CT is therefore the ideal marker for MTC and can confirm its presence at an early stage, as well as the follow up of its remission or progression/relapse/survival after surgery. There are, however, controversies such as the necessity of CT screening in patients with thyroid nodules, or particular situations causing false positive or false negative results. Our minireview also deals with an up-to-date of surgical procedures for MTC, as well as with non-surgical therapy.

Calcitonin Screening in Nodular Thyroid Disease: Is There a Definitive Answer?

Introduction: Calcitonin (Ctn) is a hormone secreted by thyroid “C” cells and is considered an excellent marker for medullary thyroid carcinoma (MTC). However, the use of Ctn to screen patients with nodular thyroid disease (NTD) remains controversial. Objective: The aim of this work was to define the frequency of hypercalcitoninemia among NTD patients followed at a tertiary referral hospital. Methods: A retrospective analysis was made of basal Ctn measurements and corresponding patients’ records between January 2011 and December 2015. Hypercalcitoninemia was defined as > 10 pg/mL. Depending on the Ctn value, three groups were considered: G1, ≤10 pg/mL; G2, 10–100 pg/mL; G3, ≥100 pg/mL. Results: Ctn was requested in an NTD context for 1,504 patients, 69 of whom had hypercalcitoninemia. Of these, 20 underwent surgery (G2, 11; G3, 9), and a histological diagnosis of MTC was established in 12 (G2, 3/27%; G3, 9/100%). Surgery was chosen based solely on Ctn levels in 7 cases, since only 5 had a positive cytology. Conclusions: Hypercalcitoninemia was found in 4.6% of NTD patients. Ctn levels ≥100 pg/mL were associated with a greater CMT risk than values between 10 and 100 pg/mL, reinforcing results from other groups. The need for an adequate interpretation of results as well as an appropriate selection of patients to surgery stresses the importance of endocrinologists requesting and interpreting results.

2016 Russian clinical practice guidelines for differentiated thyroid cancer diagnosis and treatment

В представленных клинических рекомендациях обсуждаются современные подходы к диагностике и лечению дифференцированного рака щитовидной железы у взрослых. Изменения в настоящей редакции Клинических рекомендаций касаются показаний к пункционной биопсии, скринингового определения концентрации кальцитонина, унификации заключений цитологического исследования, новых подходах к послеоперационной динамической стратификации риска рецидива, показаний к супрессивной и заместительной терапии, таргетной терапии йоднегативных форм дифференцированного рака щитовидной железы.

Should serum calcitonin be routinely measured in patients presenting with thyroid nodule?

The European Thyroid Association recommends serum calcitonin measurement in thyroid nodule cases. In contrast, the American Thyroid Association is ambivalent. In this institution, thyroid nodules cases are subject to a multidisciplinary evaluation of the clinical history and examination, ultrasound and scintigraphy, CT scan and sometimes MRI scan, biochemistry and histopathology of biopsies. We report on the current use of plasma calcitonin measurements in the context of changing practice which has not included screening of all thyroid nodules. Laboratory records were searched from the beginning of January 2010 to the end of April 2016 for all serum calcitonin measurements. There were 44 patients (30 females, age range 31 to 87 years with median 57.5) and 14 males, age range 20 to 85 years with median 53.4 years) who had a serum calcitonin measured. Of these 33 patients did not have a detectable serum calcitonin. There were 3 patients who had an initial elevated serum calcitonin which became undetectable over time. Over the same time period, a total of 2070 patients presented with thyroid nodules. Medullary thyroid cancer (MTC) was found in 7 cases. Thus assuming all MTC cases had calcitonin measured, MTC is 7 of 341 (2.05%) of the total thyroid cancer burden at the hospital and 7 of 2070 (0.338%) of all thyroid nodules. Our practice is not to routine screen all nodules for MTC. Because patients with a nodule are subjected to ultrasound scanning and biopsy, when the nodule size is greater than 5 cm or when there is a modifying ultrasound or clinical characteristic, the consensus at the multidisciplinary conference on thyroids rather than universal calcitonin screening of all nodules is the better option in our judgement.

Association of serum calcitonin levels with multinodular thyroid disease: 10-year single center experience

Background. From 2005 to 2015 routine calcitonin (CT) screening was performed in our department in all patients with multinodular goiter (MNG) using the same assay.Aim. We investigated possible associations between unstimulated serum CT levels and the presence of either thyroid autoimmunity (AITD) or thyroid neoplasia.Methods. This is a retrospective study of 648 patients (559 female [F] 86.3%, 89 male [M] 13.7%, age range 18-89, median 58 years,). CT≤4.6 pg/ml [F] and ≤11.5 pg/ml [M] was defined as normal. Patients were stratified into 4 groups according to CT. Group1: CT&lt;0.05 (undetectable), Group2: CT [F&amp;M] within normal range, Group3: CT:4.7-10 [F] &amp; 11.6-20 [M], Group4: CT&gt;10 [F] &amp; &gt;20 [M]. Furthermore patients were subcategorized in those with Autoimmune Thyroid Disease (AITD) and those without (non-AITD).Results. The distribution of patients was: Group1: n=186 (28.7%), Group2: n=422 (65.1%), Group3: n=29 (4.5%), Group4: n=11 (1.7%). Of the patients with AITD history 23.4% belonged to Group1, 68.6% to Group2, 6.4% to Group3 and 1.6% to Group4 (x2, p=0.037). Forty seven patients (7.3%) underwent total thyroidectomy. Histopathological examination revealed: Medullary Thyroid Carcinoma (MTC) n=3 (3/3 Group4), C-Cell Hyperplasia (CCH) n=5 (3/5 Group3, 2/5 Group4), Papillary Thyroid Carcinoma (PTC) n=17 (7/17 Group1, 10/17 Group2), MNG n=22 (8/22 Group1, 10/22 Group2, 2/22 Group3, 2/22 Group4). 2/5 patients with CCH had PTC. 1/17 PTC patient had mixed PTC-MTC. Patients with MTC had remarkably higher CT levels (253-1222 pg/ml) compared to those with CCH (5.8-16.1 pg/ml).Conclusions. This study reaffirms the positive correlation between CT levels and the presence of MTC or CCH, clearly and conspicuously distinguished by the range of CT levels, albeit in a small number of patients with these diagnoses. Patients with AITD have more frequently detectable or slightly increased CT levels.

Surgical cure rates of sporadic medullary thyroid cancer in the era of calcitonin screening.

Time trends of the extent of disease at first diagnosis and biochemical cure remain ill-defined for sporadic medullary thyroid cancer (MTC). This investigation aimed to delineate time trends and biochemical cure rates for sporadic MTC. This was an observational study of consecutive patients operated on for sporadic MTC between 1995 and 2015. Time trends of clinical and histopathological variables indicative of the extent of disease and biochemical cure were calculated for 600 patients with sporadic MTC, 322 of whom had initial neck surgery and 278 of whom had neck reoperation at a tertiary surgical center in Germany. From 1995-2000 to 2011-2015, significant declines (all P<0.001) were noted in the percentage of node-positive tumors (from 73 to 49%), mediastinal lymph node metastasis (from 21 to 6%) and distant metastasis (from 23 to 6%). These changes were paralleled by significant increases (all P<0.001) in mean patient age (from 49.1 to 57.3years) and the percentage of MTC ≤10mm (from 19 to 39%) and biochemical cure (from 28 to 62%). When only patients with primary tumors >10mm were considered, the decreasing percentage of mediastinal lymph node metastasis and distant metastasis, and rising mean patient age and biochemical cure rates remained statistically significant. Significant reductions in the extent of the disease and improved biochemical cure rates pointed toward increasing therapeutic control of sporadic MTC. The independent contribution of routine calcitonin screening to these time-dependent changes warrants more research.

A Genomic Alternative to Identify Medullary Thyroid Cancer Preoperatively in Thyroid Nodules with Indeterminate Cytology.

Background: The use of calcitonin screening for the rare medullary thyroid cancer (MTC) is controversial due to questions of efficacy, accuracy, and cost-effectiveness. This study reports the results of a large prospective validation using a machine-trained algorithm (MTC Classifier) to preoperatively identify MTC in fine-needle aspiration biopsies in lieu of calcitonin measurements.Methods: Cytology analysis on a prospective consecutive series of 50,430 thyroid nodule biopsies yielded a total of 7815 indeterminate (Bethesda categories III/IV) cases, which were tested with the MTC classifier. A prospective, consecutively submitted series of 2673 Bethesda III–VI cases with cytology determined locally was also evaluated. RNA was isolated and tested for the MTC Classifier using microarrays.Results: Forty-three cases were positive by the MTC Classifier among 10,488 tested nodules (0.4%), consistent with the low prevalence of MTC. Of these, all but one was histologically or biochemically confirmed as MTC, yielding a positive predictive value (PPV) of 98%. Of the positive cases, only 19 (44%) had been specifically suspected of MTC by cytology, highlighting the limitations of light microscopy to detect this disease. Three surgically confirmed MTC cases that were detected by the MTC Classifier had low basal serum calcitonin values, indicating these would have been missed by traditional calcitonin screening methods. A pooled analysis of three independent validation sets demonstrates high test sensitivity (97.9%), specificity (99.8%), PPV (97.9%), and negative predictive value (99.8%).Conclusions: A clinical paradigm is proposed, whereby cytologically indeterminate thyroid nodules being tested for common malignancies using gene expression can be simultaneously tested for MTC using the same genomic assay at no added cost.

Russian clinical practice guidelines for diagnosis and treatment of differentiated thyroid cancer

The project of Russian clinical practice guidelines for diagnosis and treatment of differentiated thyroid cancer is dedicated to the management of patients with differentiated thyroid cancer. The guideline modifications 2016 include the following matters: indication for fine-needle aspiration biopsy, calcitonin screening, standards for biopsy results, indication for suppressive therapy and thyroid replacement therapy, targeted therapy in patients with radioiodine-refractory differentiated thyroid cancer.

Thyroid C cells and their pathology: Part 2: Medullary thyroid carcinoma

All tumours with C cell differentiation are designated as medullary carcinomas (MTC). MTC occur sporadically (75-80%) or hereditary (20-25%), the latter being part of the multiple endocrine neoplasia type 2. Familial MTC, which is commonly preceded by "neoplastic" C cell hyperplasia, is caused by autosomal-dominant inherited germ line mutation of the RET-protooncogene; dependent on the codon affected by the mutation, patients show substantially different clinical courses. Due to its morphological heterogeneity, the immunohistochemical demonstration of calcitonin is mandatory for the diagnosis of MTC. For early diagnosis of MTC calcitonin screening has been introduced in Germany and Austria approx. 10 years ago in patients with thyroid nodules; however, an increased calcitonin serum level may also be caused by "non-MEN2-associated" C cell, which is not regarded as a precursor of sporadic MTC. Very rarely tumours may show a mixed C cell-follicular cell differentiation.