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    Diagnosis and pathologic characteristics of medullary thyroid carcinoma-review of current guidelines. Thomas C M,Asa S L,Ezzat S,Sawka A M,Goldstein D Current oncology (Toronto, Ont.) Background:Medullary thyroid carcinoma (mtc) is a rare malignancy of the thyroid gland, and raising awareness of the recommended diagnostic workup and pathologic characteristics of this malignancy is therefore important. Methods:We reviewed the current clinical practice guidelines and recent literature on mtc, and here, we summarize the recommendations for its diagnosis and workup. We also provide an overview of the pathology of mtc. Results:A neuroendocrine tumour, mtc arises from parafollicular cells ("C cells"), which secrete calcitonin. As part of the multiple endocrine neoplasia (men) type 2 syndromes, mtc can occur sporadically or in a hereditary form. This usually poorly delineated and infiltrative tumour is composed of solid nests of discohesive cells within a fibrous stroma that might also contain amyloid. Suspicious nodules on thyroid ultrasonography should be assessed with fine-needle aspiration (fna). If a diagnosis of mtc is made on fna, patients require baseline measurements of serum calcitonin and carcinoembryonic antigen. Calcitonin levels greater than 500 pg/mL or clinical suspicion for metastatic disease dictate the need for further imaging studies. All patients should undergo dna analysis for mutations to diagnose men type 2 syndromes, and if positive, they should be assessed for possible pheochromocytoma and hyperparathyroidism. Summary:Although the initial diagnosis of a suspicious thyroid nodule is the same for differentiated thyroid carcinoma and mtc, the remainder of the workup and diagnosis for mtc is distinct. 10.3747/co.26.5539
    Cure and survival of sporadic medullary thyroid carcinoma following systematic preoperative calcitonin screening. Torresan Francesca,Mian Caterina,Cavedon Elisabetta,Iacobone Maurizio Langenbeck's archives of surgery BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSION: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. 10.1007/s00423-019-01764-3
    CALCITONIN SECRETORY INDEX AND UNSUSPECTED NODAL DISEASE IN MEDULLARY THYROID CARCINOMA. Filimon Sabin,Payne Richard J,Black Martin J,Hier Michael P,Mlynarek Alex M,Forest Veronique-Isabelle,Tamilia Michael Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists OBJECTIVE:Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy originating from parafollicular C-cells with the potential for aggressive behavior. The extent of lymph node (LN) dissection at the time of surgery is controversial, with different schools of thought prevailing. Some systematically perform LN dissections, whereas others base their decision on radiologic evidence of disease and some with the assistance of pre-operative calcitonin (CT) levels. METHODS:We retrospectively assessed the correlation between pre-operative CT levels and clinico-pathologic factors among 42 patients with MTC between 1994 and 2015. Furthermore, we refined the use of pre-operative serum CT levels and explored for the first time a test called the Calcitonin Secretory Index (CSI, ng/mL/mm). RESULTS:Pre-operative CT levels correlated independently with tumor size ( P<.0001), number of metastatic LNs ( P<.01), and increased rates of distant metastasis. The CSI better predicted early LN disease ( P<.045). Patients with early LN metastasis had a CSI >30 ng/mL/mm, a representative threshold above which the surgical cure declines considerably. CONCLUSION:In our experience, pre-operative CT levels and now the CSI appear as sensitive and specific risk stratification markers for MTC. Despite negative findings on dedicated pre-operative neck imaging in addition to total thyroidectomy, a CSI >30 ng/mL/mm would prompt bilateral central node dissection. Due to the small sample size, our study provides preliminary evidence of the value of CSI in clinical practice. ABBREVIATIONS:ANOVA = analysis of variance; ATA = American Thyroid Association; CSI = Calcitonin Secretory Index; CT = calcitonin; LN = lymph node; MTC = medullary thyroid carcinoma; ROC = receiver operating characteristic. 10.4158/EP-2017-0236
    Prediction of lateral neck lymph node metastasis according to preoperative calcitonin level and tumor size for medullary thyroid carcinoma. Bae Soo Y,Jung Seung P,Choe Jun-Ho,Kim Jee S,Kim Jung H The Kaohsiung journal of medical sciences Medullary thyroid carcinoma (MTC) accounts up to 10% of all thyroid cancers, but is responsible for a disproportionate number of deaths. While surgery is the only curative treatment for MTC, indications for lateral neck lymph node (LLN) dissection are controversial. We performed a retrospective review to describe clinical outcomes in 93 MTC patients from July 1995 to March 2015. We analyzed their clinicopathologic factors, and cut-off values of tumor size and calcitonin levels were calculated using a receiver operating characteristic curve. Using the instances of lymph node metastases, the tumor size cut-off value was 0.95 cm (area under curve, AUC = 0.697) in patients with ipsilateral central lymph node (CLN) metastases, 2.25 cm (AUC = 0.793) in contralateral CLN metastases, and 1.75 cm (AUC = 0.753) in ipsilateral LLN metastases. The cut-off values of preoperative calcitonin levels were 226.6 pg/mL (AUC = 0.746) in ipsilateral CLN, 755.0 pg/mL (AUC = 0.840) in contralateral CLN metastases, and 237.0 pg/mL (AUC = 0.775) in ipsilateral LLN metastases. This study supports the notion that ipsilateral LLN metastases occur before contralateral CLN metastases. Therefore, ipsilateral LLN dissection should be considered in patients with contralateral CLN metastases. The extent of surgery should be based on the status of LN metastases, preoperative basal calcitonin level, and tumor size to help individualize the extent of surgery. 10.1002/kjm2.12122
    Procalcitonin as a postoperative marker in the follow-up of patients affected by medullary thyroid carcinoma. Trimboli Pierpaolo,Lauretta Rosa,Barnabei Agnese,Valabrega Stefano,Romanelli Francesco,Giovanella Luca,Appetecchia Marialuisa The International journal of biological markers AIM:Due to the limits of calcitonin, other markers are warranted to better manage medullary thyroid carcinoma patients, and procalcitonin has been reported as promising. Here we aimed to evaluate procalcitonin as a marker of medullary thyroid carcinoma in the post-treatment follow-up. METHODS:Medullary thyroid carcinoma patients previously treated by thyroidectomy were enrolled. After complete imaging work-up (i.e. ultrasonography, computed tomography, magnetic resonance and FDG-PET-CT) we identified patients with structural recurrent/persistent medullary thyroid carcinoma (active medullary thyroid carcinoma) and subjects with no evidence of disease. Then, both calcitonin and procalcitonin were measured and their performance analyzed. RESULTS:The final series included 55 medullary thyroid carcinoma patients treated and followed-up for about five years. Of these, 43 were assessed as no evidence of disease, and 12 as active medullary thyroid carcinoma. The median value of procalcitonin was significantly higher ( P < 0.0001) in active medullary thyroid carcinoma patients (3.10 ng/mL) than in those with no evidence of disease (0.10 ng/mL). Also, calcitonin levels of active medullary thyroid carcinoma (96.7 pg/mL) were significantly ( P < 0.0001) higher than that of no evidence of disease (2.0 pg/mL). At the receiver operating characteristic curve analysis, the optimal cut-off of procalcitonin was ≥0.32 ng/mL with 92% sensitivity and 98% specificity, while the most accurate threshold of calcitonin was ≥12.0 pg/mL with 100% sensitivity and 91% specificity. There was no active medullary thyroid carcinoma with simultaneously negative results of procalcitonin and calcitonin. CONCLUSIONS:Procalcitonin is reliable in discriminating medullary thyroid carcinoma patients with active disease from those with no evidence of disease. We suggest using procalcitonin as complementary to calcitonin to follow-up medullary thyroid carcinoma patients. 10.1177/1724600817747518
    [Clinical significance and cost-benefit analysis of serum calcitonin assay in diagnosis and treatment of medullary thyroid carcinoma]. Hao W J,Zhang H,Yu Y,Zhao J,Ge Z J,Ding P X,Sun X X,Liu H,Wen S Y,You J Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery To study the clinical significance of serum calcitonin in the diagnosis and treatment of medullary thyroid carcinoma and to analyze its cost-benefit. One hundred and forty one patients with medullary thyroid carcinoma who undertook calcitonin test and frozen pathological examination were enrolled in this study from Oct 2012 to Mar 2018. Using the method of χ(2) test, the positive rate of calcitonin test and frozen pathological examination in diagnosis of medullary thyroid carcinoma(MTC) were compared. Firstly, we compared the correct checkout cost of calcitonin test and that of frozen pathological examination (total number of patients×cost of examination/the correctly detected number of patients) . Secondly, we calculated whether calcitonin test help patients save money(average cost of treatment in hospital for MTC×number of patients who were evaluated to be candidate for surgery-cost of calcitonin test×total number of patients)/total number of patients. 139 patients were positive in calcitonin test among 141 patients, and the positive rate was 98.58%. 91 patients were positive in frozen pathological examination, and the positive rate was 64.54% (χ(2)=97.821, 0.000 1) . Cost-benefit analysis showed that the correct checkout cost of calcitonin test and frozen pathological examination were 71.01 yuan and 426.10 yuan, also,1 371 938.64 yuan could be saved totally and 9 730.06 yuan could be saved per patient because of calcitonin test. Serum calcitonin test had a significant effect on the diagnosis and treatment of medullary thyroid carcinoma and was economical and practical. 10.3760/cma.j.issn.1673-0860.2019.07.005
    Calcitonin negative Medullary Thyroid Carcinoma: a challenging diagnosis or a medical dilemma? Gambardella Claudio,Offi Chiara,Patrone Renato,Clarizia Guglielmo,Mauriello Claudio,Tartaglia Ernesto,Di Capua Francesco,Di Martino Sergio,Romano Roberto Maria,Fiore Lorenzo,Conzo Alessandra,Conzo Giovanni,Docimo Giovanni BMC endocrine disorders BACKGROUND:Medullary thyroid carcinoma is a neuroendocrine tumor belonging form a malignant growth of the thyroid parafollicular C-cells, representing from 1 to 10% of all thyroid cancer. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryogenic antigen, which are sensitive tumor markers, facilitating the diagnosis, follow-up and prognostication. The diagnosis is reached through the identification of high basal calcitonin serum level or after pentagastrin stimulation test. Medullary thyroid carcinoma is able to produce other relevant biomarkers as procalcitonin, carcinoembryionic antigen and chromogranin A. In Literature are described few cases of medullary thyroid carcinoma without elevation of serum calcitonin, an extremely rare event. The aim of this study was to analyse the presentation, the main features and therapeutic management of medullary thyroid carcinoma associated with negative serum calcitonin levels. METHODS:Using the PubMed database, a systematic review of the current Literature was carried out, up to February 2018. Finally, nineteen articles met our inclusion criteria and were selected according to the modified Newcastle-Ottawa scale. RESULTS:Fourty-nine patients with definitive pathology confirming medullary thyroid carcinoma and with calcitonin serum level in the normal range were identified (24 female, 24 male and not reported gender in 1 case). Mean age was 51.7 years. Serum calcitonin levels were reported for 20 patients with a mean value of 8.66 pg/mL and a range of 0.8-38 pg/mL. Despite the low or undetectable calcitonin serum level, at immunochemistry in almost the half of the cases reported by the Authors, the tumors presented diffuse or focal positivity for calcitonin and carcinoembryionic antigen, while was reported a chromogranin A positivity in 41 of the 43 tested patients. CONCLUSIONS:Calcitonin negative medullary thyroid carcinoma is an extremely rare pathology. The diagnosis and the surveillance is often challenging and delayed, due to the lack of elevation of serum markers as calcitonin and carcinoembryionic antigen. Further studies are needed, to better define options for management of non secretory medullary thyroid carcinoma and to identify new and reliable biomarkers associated to diagnosis and relapse of this medical dilemma. 10.1186/s12902-019-0367-2