Search

Simple Summary: Total thyroidectomy and dissection of cervical lymph node compartments, depending on serum calcitonin levels and ultrasound findings, is standard treatment for patients with medullary thyroid cancer. The aim of this study was to evaluate whether pre-operative calcitonin and CEA levels can be useful as biomarkers of the extent of lymph node metastases at diagnosis. Results indicate that pre-operative serum calcitonin and CEA levels can predict presence, number, and site of lymph node metastases and, more specifically, values of 90 pg/mL for calcitonin and 17 ng/mL for CEA accurately indicate the N1b status. Since surgery is the only curative treatment for medullary thyroid cancer and there is not a strong indication regarding the extent of lymphadenectomy, these findings may help in the choice of the extent of neck dissection. Background: In medullary thyroid cancer (MTC), lymph node metastases are often present at diagnosis and the extent of surgery is usually based upon pre-operative calcitonin and CEA levels as well as ultrasound findings. The aim of this study was to evaluate the role of pre-operative calcitonin and CEA levels as predictive markers of the burden of lymph node metastases at diagnosis. Methods: we conducted a retrospective study analyzing 87 MTC patients. Results: The median levels of calcitonin and CEA were 88.4 pg/mL and 7.0 ng/mL, respectively, in patients with no lymph nodes metastases; 108.0 pg/mL and 9.6 ng/mL, respectively, in patients with metastases to 1–5 lymph nodes; 520.5 pg/mL and 43.2 ng/mL, respectively, in patients with metastases to >5 lymph nodes. There were no significant differences in pre-operative calcitonin and CEA values between N0 and N1a patients, whereas they were significantly higher in N1b patients. Pre-operative cut-off levels distinguishing N0/N1a from N1b patients were 90 pg/mL for calcitonin (sensitivity 100%, specificity 59.3%, AUC = 0.82) and 17 ng/mL for CEA (sensitivity 100%, specificity 75%, AUC = 0.89). Conclusions: in patients with MTC, pre-operative serum calcitonin and CEA levels may drive the decision-making process to better define the extent of surgery. [ABSTRACT FROM AUTHOR]

Background: The concomitant presence of papillary thyroid cancer (PTC) and medullary TC (MTC) is rare. In this multicentric study, we documented the epidemiological characteristics, disease conditions and clinical outcome of patients with simultaneous MTC/PTC. Methods: We collected data of patients with concomitant MTC/PTC at 14 Italian referral centers. Results: In total, 183 patients were enrolled. Diagnosis was mostly based on cytological examination (n = 58, 32%). At diagnosis, in the majority of cases, both PTC (n = 142, 78%) and MTC (n = 100, 54%) were at stage I. However, more cases of stage II–IV were reported with MTC (stage IV: n = 27, 15%) compared with PTC (n = 9, 5%). Information on survival was available for 165 patients: 109 patients (66%) were disease-free for both PTC and MTC at the last follow-up. Six patients died from MTC. Median time to progression was 123 months (95% confidence interval (CI): 89.3–156.7 months). Overall, 45% of patients were disease-free after >10 years from diagnosis (125 months); this figure was 72.5% for PTC and 51.1% for MTC. Conclusions: When MTC and PTC are concurrent, the priority should be given to the management of MTC since this entity appears associated with the most severe impact on prognosis. [ABSTRACT FROM AUTHOR]

Applying genetic screening in medullary thyroid cancer (MTC) patients we identified an unexpectedly high frequency of c.2671T>G, p.Ser891Ala RET mutation carriers. Our aim was to: (a) deeply characterize the clinical expression of this mutation, (b) identify the presence of a founder effect in our region. Genetic analysis was performed in 251 relatives from 28 Ser891Ala kindreds, among 108 p.Ser891Ala asymptomatic carriers, 64 were submitted to thyroidectomy: mean age for 10 subjects presenting C-cells hyperplasia was 30.2 ± 13.7 years, raising to 37.9 ± 10.3 in 14 subjects with micro-MTC and to 55.0 ± 14.7 years in 39 subjects with MTC. Age-related progression across histopathological groups CCH/microMTC and MTC were statistically significant: genetic screening in Ser891Ala families could be safely postponed at the age of 14. To investigate the hypothesis of a common ancestor for Ser891Ala mutation we genotyped for 18 polymorphic microsatellite markers encompassing RET locus all subjects belonging to Ser891Ala families and we identified a founder effect, estimating the age of a common ancestor, dating back to 1493 AD. Ethnographic data collected in historical archives support laboratory results; the high prevalence of this mutation in our region could suggest the hypothesis of a population study to realize a preventive intervention in a rare neoplastic disease., (© 2019 Wiley Periodicals, Inc.)

BACKGROUND Around 25% of all cases of medullary thyroid cancer (MTC) arise as part of the hereditary multiple endocrine neoplasia type 2 (MEN2) syndrome, which is characterized by activating point mutations in the RET proto-oncogene. The remaining 75% of cases are sporadic. OBJECTIVE To report the results of genetic screening for RET mutations performed at a single Italian center over a 13 year period. DESIGN AND INTERVENTION This study enrolled individuals who presented with sporadic or hereditary MTC between 1993 and 2006. First-degree relatives of patients with hereditary disease were also invited to enroll. Genomic DNA was isolated from peripheral blood lymphocytes and subjected to genetic screening for RET mutations. Exons 10, 11, 13, 14, 15, and 16 were analyzed by polymerase chain reaction and DNA sequencing. Patients with MTC and individuals found to be RET mutation carriers were screened annually for clinical and biochemical signs for thyroid, parathyroid and adrenal gland involvement. MTC was confirmed by histological appearance and the presence of cells that stained positive for calcitonin and chromogranin. OUTCOME MEASURES The main outcome measures were the identification of germline RET mutations and the genotype-phenotype correlation. RESULTS Genetic screening was performed in 481 patients with sporadic MTC (60% female; median age 51 years), 37 patients with hereditary MTC (59% female; median age 31 years), and 289 first-degree relatives (50% female; median age 31 years). Clinical follow-up was for 1-25 years. Germline RET mutations were identified in 35 patients who presented with sporadic MTC (7.3%). Mutations in these patients were distributed across several exons; however, non-cysteine-encoding codons were affected in 23 cases (65.7%). In 34 of these patients, MTC was the only endocrine tumor detected (mean followup 8.1 years). Pheochromocytoma was detected 6 years after the initial diagnosis of MTC in the remaining case. By contrast, RET mutations were identified in 36 patients who presented with hereditary MTC (97%). Of these, only 12.9% were detected in non-cysteine-encoding codons. The prevalence of mutations in non-cysteine-encoding codons was, therefore, significantly greater in cases of familial MTC originally diagnosed as sporadic disease than in cases that originally presented as familial MTC (P<0.0001). When all cases of hereditary MTC with mutations in non-cysteine-encoding codons were considered together, the most common mutation was at codon 804 (14 of 27 cases [51.8%]), which results in a substitution of valine to methionine. When genotype was correlated with phenotype, the 72 families with hereditary disease analyzed in this study were characterized as follows: familial MTC (45 families [62.5%]), MEN2A (22 families [30.5%]) and MEN2B (5 families [7.0%]). CONCLUSION Hereditary disease was identified in 7.3% of the apparently sporadic cases of MTC. A strong association between familial MTC previously diagnosed as sporadic disease and RET mutations in non-cysteine-encoding codons was reported. [ABSTRACT FROM AUTHOR]