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Nature Reviews. Endocrinology Nov 2016During the past few decades, the incidence of thyroid cancer has increased substantially in many countries, including the USA. The rise in incidence seems to be... (Review)
Review
During the past few decades, the incidence of thyroid cancer has increased substantially in many countries, including the USA. The rise in incidence seems to be attributable both to the growing use of diagnostic imaging and fine-needle aspiration biopsy, which has led to enhanced detection and diagnosis of subclinical thyroid cancers, and environmental factors. The latest American Thyroid Association (ATA) practice guidelines for the management of adult patients with thyroid nodules and differentiated thyroid cancer differ substantially from the previous ATA guidelines published in 2009. Specifically, the problems of overdiagnosis and overtreatment of a disease that is typically indolent, where treatment-related morbidity might not be justified by a survival benefit, now seem to be acknowledged. As few modifiable risk factors for thyroid cancer have been established, the specific environmental factors that have contributed to the rising incidence of thyroid cancer remain speculative. However, the findings of several large, well-designed epidemiological studies have provided new information about exposures (such as obesity) that might influence the development of thyroid cancer. In this Review, we describe the changing incidence of thyroid cancer, suggest potential explanations for these trends, emphasize the implications for patients and highlight ongoing and potential strategies to combat this growing clinical and public health issue.
Topics: Adenocarcinoma, Follicular; Age Distribution; Biopsy, Fine-Needle; Carcinoma; Carcinoma, Neuroendocrine; Carcinoma, Papillary; Humans; Incidence; Medical Overuse; Obesity; Radiation Exposure; Risk Factors; Sex Distribution; Smoking; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Thyroid Nodule; United States
PubMed: 27418023
DOI: 10.1038/nrendo.2016.110 -
Journal of Clinical Oncology : Official... Jan 2022Medullary thyroid carcinoma (MTC) is an aggressive neuroendocrine tumor (NET) arising from the calcitonin-producing C cells. Unlike other NETs, there is no widely...
PURPOSE
Medullary thyroid carcinoma (MTC) is an aggressive neuroendocrine tumor (NET) arising from the calcitonin-producing C cells. Unlike other NETs, there is no widely accepted pathologic grading scheme. In 2020, two groups separately developed slightly different schemes (the Memorial Sloan Kettering Cancer Center and Sydney grade) on the basis of proliferative activity (mitotic index and/or Ki67 proliferative index) and tumor necrosis. Building on this work, we sought to unify and validate an internationally accepted grading scheme for MTC.
PATIENTS AND METHODS
Tumor tissue from 327 patients with MTC from five centers across the United States, Europe, and Australia were reviewed for mitotic activity, Ki67 proliferative index, and necrosis using uniform criteria and blinded to other clinicopathologic features. After reviewing different cutoffs, a two-tiered consensus grading system was developed. High-grade MTCs were defined as tumors with at least one of the following features: mitotic index ≥ 5 per 2 mm, Ki67 proliferative index ≥ 5%, or tumor necrosis.
RESULTS
Eighty-one (24.8%) MTCs were high-grade using this scheme. In multivariate analysis, these patients demonstrated decreased overall (hazard ratio [HR] = 11.490; 95% CI, 3.118 to 32.333; < .001), disease-specific (HR = 8.491; 95% CI, 1.461 to 49.327; = .017), distant metastasis-free (HR = 2.489; 95% CI, 1.178 to 5.261; = .017), and locoregional recurrence-free (HR = 2.114; 95% CI, 1.065 to 4.193; = .032) survivals. This prognostic power was maintained in subgroup analyses of cohorts from each of the five centers.
CONCLUSION
This simple two-tiered international grading system is a powerful predictor of adverse outcomes in MTC. As it is based solely on morphologic assessment in conjunction with Ki67 immunohistochemistry, it brings the grading of MTCs in line with other NETs and can be readily applied in routine practice. We therefore recommend grading of MTCs on the basis of mitotic count, Ki67 proliferative index, and tumor necrosis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biopsy; Carcinoma, Neuroendocrine; Cell Proliferation; Child; Child, Preschool; Consensus; Europe; Female; Humans; Ki-67 Antigen; Male; Middle Aged; Mitotic Index; Necrosis; Neoplasm Grading; New South Wales; Predictive Value of Tests; Reproducibility of Results; Retrospective Studies; Risk Assessment; Risk Factors; Thyroid Neoplasms; United States; Young Adult
PubMed: 34731032
DOI: 10.1200/JCO.21.01329 -
The New England Journal of Medicine Sep 2016
Review
Topics: Carcinoma; Carcinoma, Medullary; Carcinoma, Papillary; Humans; Mutation; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 27626519
DOI: 10.1056/NEJMra1501993 -
Journal of Veterinary Diagnostic... Nov 2022A 12-y-old, castrated male Weimaraner dog was presented for a wellness examination. A 7-cm, firm mass was palpated on the left, ventral, mid-lateral neck. The neck mass...
A 12-y-old, castrated male Weimaraner dog was presented for a wellness examination. A 7-cm, firm mass was palpated on the left, ventral, mid-lateral neck. The neck mass was removed surgically and submitted for histopathology. A thyroid carcinoma was diagnosed based on microscopic examination. Immunohistochemistry for chromogranin-A, calcitonin, and thyroglobulin identified dual immunoreactivity of the latter two, and a final diagnosis was of a well-differentiated, compact, mixed medullary and follicular cell thyroid carcinoma. These neoplasms are rare in humans and have not been reported in dogs, to our knowledge.
Topics: Humans; Dogs; Male; Animals; Thyroglobulin; Calcitonin; Carcinoma, Medullary; Chromogranins; Adenocarcinoma, Follicular; Thyroid Neoplasms; Dog Diseases
PubMed: 36127830
DOI: 10.1177/10406387221126655 -
Frontiers in Endocrinology 2022Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine neoplasm that may spread to lymph nodes before the primary tumor is diagnosed; moreover, distant... (Review)
Review
CONTEXT
Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine neoplasm that may spread to lymph nodes before the primary tumor is diagnosed; moreover, distant metastases are already present in about 10% of patients at diagnosis. Serum calcitonin (Ctn) usually reflects the spread of disease, thus orienting the extent of surgery and predicting the possibility of biochemical remission. Tumor size and vascular invasion are important prognostic factors, but little is known on the relationship between other histopathological features, such as the presence of a tumor capsule, and long term outcome of MTC.
PURPOSE
To evaluate the prevalence of encapsulated tumors among MTCs and the association of tumor capsule with a favorable outcome after surgery.
METHODS
A retrospective observational single-center study was conducted together with a narrative review of the available literature.
RESULTS
Among 44 patients (27 female, 17 male; median age: 56 years) with MTC (6 hereditary, 37 sporadic) followed up at our center in the last four years (median follow-up: 29.2 months), seven (15.9%) showed an encapsulated tumor at histology and a clinical remission after surgery. None of them had nodal metastases and median preoperative Ctn (398 pg/mL, IQR 126.5-7336) did not differ significantly from that of the 14 patients (31.8%) with persistent disease after surgery (787 pg/mL, IQR 340.5-2905.5; p=0.633), although their tumor size was significantly higher (median 33 mm versus 16 mm respectively, p=0.036). Among patients with preoperative Ctn levels above 500 pg/mL (n=11), only two (18.2%) showed undetectable Ctn levels during follow-up, both having an encapsulated MTC (OR 0.000, p=0.02). Notably, they were two similar cases of large MTC (> 3 cm) with extensive hyalinization and calcification, associated with very high Ctn levels (> 13'500 and 1'100 pg/mL, respectively) but no nodal nor distant metastases, in complete remission after surgery although one of them carried the aggressive M918T somatic mutation.
CONCLUSION
MTC rarely shows a tumor capsule, which seems to correlate with a better prognosis and absence of nodal metastases, regardless of or mutational status. Among encapsulated MTCs (E-MTC), Ctn levels and tumor size are not predictive of persistence of disease after surgery.
Topics: Carcinoma, Neuroendocrine; Female; Humans; Male; Middle Aged; Prognosis; Retrospective Studies; Thyroid Neoplasms
PubMed: 35574005
DOI: 10.3389/fendo.2022.866572 -
Asian Pacific Journal of Cancer... 2015Thyroid cancer is the most common endocrine neoplasia. The medullary thyroid carcinoma (MTC) is one of the most aggressive forms of thyroid malignancy,accounting for up... (Review)
Review
Thyroid cancer is the most common endocrine neoplasia. The medullary thyroid carcinoma (MTC) is one of the most aggressive forms of thyroid malignancy,accounting for up to 10% of all types of this disease. The mode of inheritance of MTC is autosomal dominantly and gain of function mutations in the RET proto-oncogene are well known to contribute to its development. MTC occurs as hereditary (25%) and sporadic (75%) forms. Hereditary MTC has syndromic (multiple endocrine neoplasia type 2A, B; MEN2A, MEN2B) and non-syndromic (Familial MTC, FMTC) types. Over the last two decades, elucidation of the genetic basis of tumorigenesis has provided useful screening tools for affected families. Advances in genetic screening of the RET have enabled early detection of hereditary MTCs and prophylactic thyroidectomy for relatives who may not show any symptom sof the disease. In this review we emphasize the main RET mutations in syndromic and non syndromic forms of MTC, and focus on the importance of RET genetic screening for early diagnosis and management of MTC patients, based on American Thyroid Association guidelines and genotype-phenotype correlation.
Topics: Carcinoma, Neuroendocrine; Early Detection of Cancer; Humans; Mutation; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret; Thyroid Neoplasms
PubMed: 25824727
DOI: 10.7314/apjcp.2015.16.6.2107 -
Journal of Ayub Medical College,... 2018Medullary thyroid carcinoma (MTC) is a relatively rare thyroid malignancy and its clinical course varies among patients due to its familial association. A number of...
BACKGROUND
Medullary thyroid carcinoma (MTC) is a relatively rare thyroid malignancy and its clinical course varies among patients due to its familial association. A number of prognostic factors have been studied, but the significance of these factors remains controversial. We evaluated the progression free survival (PFS) and overall survival (OS) of MTC and its association with tumour marker rising velocity and serum calcitonin (Ct) doubling time (DT).
METHODS
Analysis of 83 (8.7%) consecutive MTC patients registered at a single centre between 1995 and 2015. The impact of tumour respectability, TNM stage, multiple endocrine neoplasia (MEN) syndrome, local recurrence, Ct DT and Ct rising velocity on PFS and OS was analysed. Median follow-up was 4.3 years (range: 1-18 years).
RESULTS
Eighty-three (8.7%) of all thyroid cancers registered at our centre were MTC. Fifty-five males, 28 females. Mean age 39 years [range: 17-72 years]. Twenty-two were unresectable and 61 resectable. Five-year and 10-year OS was 84% and 77% respectively. Of 68 with follow up greater than a year; 20 (29.4%) were cured, 15 (22.1%) had biochemical evidence of disease, three (4.4%) had stable macroscopic disease and 30 (44.1%) had recurrent/progressive disease. Sixteen (23.5%) died. On multivariate analysis, T4 tumour, male gender, nodal and distant metastases, tumour resectibility, Ct DT less than two years and tumour marker rising velocity of greater than 0.05pg/ml/month were poor prognostic factors (pvalue <0.05). Age and association with MEN syndrome had no statistically significant survival impact. Radiotherapy reduced local relapse in patients with nodal disease. Total thyroidectomy with nodal clearance lessened relapses.
CONCLUSION
Clinical stage and pathological aspects are predictors of disease progression. Persistent biochemical evidence of MTC does not affect OS, however, Ct DT < 2 years and rapid rate of tumour marker rise predict disease progression.
Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Calcitonin; Carcinoma, Neuroendocrine; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Multiple Endocrine Neoplasia; Neoplasm Recurrence, Local; Neoplasm Staging; Progression-Free Survival; Survival Rate; Thyroid Neoplasms; Thyroidectomy; Young Adult
PubMed: 30838820
DOI: No ID Found -
Current Oncology (Toronto, Ont.) Nov 2023Papillary thyroid carcinoma (PTC) is the most common type of differentiated TC, while medullary TC (MTC) accounts for 4%. The concomitant presence of PTC and MTC is rare. (Review)
Review
BACKGROUND
Papillary thyroid carcinoma (PTC) is the most common type of differentiated TC, while medullary TC (MTC) accounts for 4%. The concomitant presence of PTC and MTC is rare.
METHODS
This is a retrospective, single-center observational study conducted over 16 years (2001-2017). The data were collected from the clinical records of patients who underwent total thyroidectomy at the Endocrine Unit-Department of Medicine of the University Hospital of Pisa, Italy.
RESULTS
Over 690 analyzed cases, 650 (94.2%) were exclusive DTC, 19 exclusive MTC (2.75%) and 5 PTC/MTC (0.7%). No case of mixed medullary/follicular TC or hereditary MTC (familial MTC/multiple endocrine neoplasia type 2) was found. Among the five PTC/MTC cases, there was a male prevalence (M:F = 3:2), and all PTC components were at stage I, whereas 40% of MTC were at stage I and III and 20% of MTC were at stage II; microPTC (mPTC) was prevalent (80%) and also microMTCs were frequent (40%); 60% of MTC patients recovered, while 40% of patients developed metastatic disease. The search for germline mutations of the RET gene resulted in being negative in all cases.
CONCLUSIONS
The incidence of PTC/MTC has been increasing over the past 30 years. The etiology of PTC/MTC forms is still unknown, and although this simultaneous occurrence could be only a coincidence, we cannot exclude the hypothesis of a shared genetic origin.
Topics: Humans; Male; Carcinoma, Medullary; Carcinoma, Papillary; Observational Studies as Topic; Proto-Oncogene Proteins c-ret; Retrospective Studies; Thyroid Cancer, Papillary; Thyroid Neoplasms; Female
PubMed: 38132379
DOI: 10.3390/curroncol30120745 -
Journal of Endocrinological... Dec 2023The determination of tumour biomarkers is paramount to advancing personalized medicine, more so in rare tumours like medullary thyroid carcinoma (MTC), whose diagnosis...
PURPOSE/METHODS
The determination of tumour biomarkers is paramount to advancing personalized medicine, more so in rare tumours like medullary thyroid carcinoma (MTC), whose diagnosis is still challenging. The aim of this study was to identify non-invasive circulating biomarkers in MTC. To achieve this goal, paired MTC tissue and plasma extracellular vesicle samples were collected from multiple centres and microRNA (miRNA) expression levels were evaluated.
RESULTS
The samples from a discovery cohort of 23 MTC patients were analysed using miRNA arrays. Lasso logistic regression analysis resulted in the identification of a set of circulating miRNAs as diagnostic biomarkers. Among them, miR-26b-5p and miR-451a, were highly expressed and their expression decreased during follow-up in disease-free patients in the discovery cohort. Circulating miR-26b-5p and miR-451a were validated using droplet digital PCR in a second independent cohort of 12 MTC patients.
CONCLUSION
This study allowed the identification and validation of a signature of two circulating miRNAs, miR-26b-5p and miR-451a, in two independent cohorts reporting a significant diagnostic performance for MTC. The results of this study offer advancements in molecular diagnosis of MTC proposing a novel non-invasive tool to use in precision medicine.
Topics: Humans; MicroRNAs; Thyroid Neoplasms; Circulating MicroRNA; Biomarkers; Biomarkers, Tumor
PubMed: 37286863
DOI: 10.1007/s40618-023-02115-2 -
Head & Neck Feb 2021Medullary thyroid carcinoma (MTC) is a rare malignancy with high incidence of cervical lymph node (CLN) metastasis. We investigated the impact of nodal disease burden on...
BACKGROUND
Medullary thyroid carcinoma (MTC) is a rare malignancy with high incidence of cervical lymph node (CLN) metastasis. We investigated the impact of nodal disease burden on survival.
METHODS
We searched the National Cancer Database for MTC patients treated surgically. Impact of nodal metastasis on survival was analyzed using Cox univariable and multivariable regression.
RESULTS
We identified 2627 patients from 2004 to 2015. Positive CLNs were identified in 1433 (54.5%), and 542 (20.6%) had >10 CLN+. Overall survival was 94.5% and 89.6% at 3 and 5 years. Patients with 11 to 20 CLN+ had significantly worse survival than patients with 1 to 10 CLN+ in univariable and multivariable analyses (HR = 3.56 (2.31-5.50) vs 2.26 (1.60-3.20); P < .0001). The ratio of positive to dissected CLN was associated with overall survival.
CONCLUSIONS
Higher burden of nodal disease is associated with worse survival in MTC. The number of positive nodes could be a valuable prognosticator in addition to the current staging system.
Topics: Carcinoma, Neuroendocrine; Cost of Illness; Humans; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Prognosis; Thyroid Neoplasms
PubMed: 33107153
DOI: 10.1002/hed.26511