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Journal of Endocrinological... Jan 2024Expression of the programmed death-ligand 1 (PD-L1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) in medullary thyroid carcinoma (MTC) has been...
PURPOSE
Expression of the programmed death-ligand 1 (PD-L1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) in medullary thyroid carcinoma (MTC) has been controversial and rarely reported.
METHODS
Surgical specimens of 190 MTC patients who had initial curative-intent surgery were collected. Immunohistochemistry of PD-L1 and TIM-3 was performed using 22C3 pharmDx (Dako, Carpinteria, CA) and anti-TIM-3 (1:500, ab241332, Abcam). Stained slides were scored using a combined positive score (CPS) with a cutoff of ≥ 1. We established correlations between PD-L1 expression, TIM-3 expression, clinicopathological, and survival data.
RESULTS
13 cases (13/190, 6.84%) were positive for PD-L1 expression, and 42 cases (42/154, 27.27%) for TIM-3 expression. PD-L1 expression was correlated to TIM-3 expression (P = 0.002), but was not related to overall survival (OS) or progression-free survival (PFS). TIM-3 expression was correlated to perineural invasion (P = 0.040). Multivariate Cox analysis showed that lymphovascular invasion (LVI) was independently associated with OS. And tumor size, LVI, and lymph node metastases were significantly associated with PFS. Furthermore, the multivariate logistic analysis showed multifocal status, LVI, pathological T stage and lymph node metastasis were independent risk factors for biochemical recurrence/persistent disease.
CONCLUSIONS
We demonstrated that PD-L1 and TIM-3 expression were not frequent in MTC and were not associated with survival prognosis. Our results should be considered when clinical trials of PD-L1 or TIM-3 blockades are implemented.
Topics: Humans; Prognosis; Immunohistochemistry; B7-H1 Antigen; Retrospective Studies; Hepatitis A Virus Cellular Receptor 2; Thyroid Neoplasms; Lymphatic Metastasis; Biomarkers, Tumor
PubMed: 37464189
DOI: 10.1007/s40618-023-02126-z -
World Journal of Surgery Aug 2021The purpose of the article was to evaluate the existence of significant clinical, pathological and prognostic differences between familial and sporadic form of pediatric...
BACKGROUND
The purpose of the article was to evaluate the existence of significant clinical, pathological and prognostic differences between familial and sporadic form of pediatric non-medullary thyroid carcinoma, in order to tailor the therapeutic strategy to be adopted for patients with family history.
METHODS
We analyzed the records of 76 pediatric patients that underwent surgery for differentiated thyroid cancer from 2014 to 2019 at the Surgical Pathology Department of the University of Pisa, Italy. Among these, 20 (26,3%) had positive family history (familial non-medullary thyroid carcinoma-FNMTC group) while 56 (73.7%) were affected by sporadic forms (sporadic non-medullary thyroid carcinoma-SNMTC group).
RESULTS
In our study, the correlation between the FNMTC and the SNMTC group showed no difference in terms of tumor features like multifocality, bilaterality, capsular/extracapsular invasion and the presence of vascular emboli. A statistical significance, on the other hand, was revealed by observation of clinical outcomes, such as distant metastasis (p = 0,022), persistence of disease (p = 0,054) and necessity of radioiodine sessions (p = 0,005).
CONCLUSIONS
These findings suggest that family history may have an independent role on the outcome, expressing its action through an intrinsic more aggressive biological behavior. Therefore, familial non-medullary thyroid carcinoma in children represents a nosological entity that requires an accurate pre-operative evaluation, an adequate surgical strategy and a careful follow up.
Topics: Child; Humans; Iodine Radioisotopes; Retrospective Studies; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroidectomy
PubMed: 33891138
DOI: 10.1007/s00268-021-06104-5 -
Medicine Dec 2017Medullary thyroid carcinoma (MTC) is a rare type thyroid carcinoma originating from the thyroid parafollicular cells (C cells). Chemotherapy has a limited efficacy for... (Review)
Review
RATIONALE
Medullary thyroid carcinoma (MTC) is a rare type thyroid carcinoma originating from the thyroid parafollicular cells (C cells). Chemotherapy has a limited efficacy for treating persistent or recurrent MTC.
PATIENT CONCERNS
A 46-year-old woman who underwent thyroidectomy for MTC in December 2007. She began experience recurring diarrhea in January 2015 and started to cough and feel shortness of breath in March 2016.
DIAGNOSES
A chestcomputed tomography (CT) scan showed metastases in the bilateral lungs, pulmonary hilum, and mediastinal lymph nodes. Percutaneous biopsy of the pulmonary occupying lesions performed on March 21, 2016 indicated medullary carcinoma metastases at the right pulmonary hilum.
INTERVENTIONS
This patient was treated with oral apatinib (500 mg daily).
OUTCOMES
The patient's symptoms of diarrhea, coughing, and shortness of breath disappeared. CT reexaminations for efficacy assessment at 1, 2, and 3 months after the treatment indicated partial remission. Systemic migrating bone and joint pains occurred during the treatment, which were considered to be adverse events of apatinib.
LESSONS
Treatment of MTC with apatinib has been shown to be effective in our case. Tyrosine kinase inhibitors (TKIs) that suppress rearranged during transfection (RET) and vascular endothelial growth factor receptor (VEGFR) should be considered as a effective therapeutic approaches.
Topics: Carcinoma, Neuroendocrine; Female; Humans; Lung Neoplasms; Middle Aged; Protein Kinase Inhibitors; Pyridines; Thyroid Neoplasms; Thyroidectomy
PubMed: 29390263
DOI: 10.1097/MD.0000000000008704 -
Surgery Sep 2021Unlike medullary thyroid carcinoma in adults, the vast majority of pediatric medullary thyroid carcinoma is hereditary. Pediatric medullary thyroid carcinoma is known to...
BACKGROUND
Unlike medullary thyroid carcinoma in adults, the vast majority of pediatric medullary thyroid carcinoma is hereditary. Pediatric medullary thyroid carcinoma is known to have different genetic alterations driving tumorigenesis, but it is not known if pediatric medullary thyroid carcinoma has different clinicopathologic features. This study aims to identify which pediatric medullary thyroid carcinoma patients might warrant elective neck dissection.
METHODS
We selected all patients ages 0 to 19 diagnosed with clinically evident medullary thyroid carcinoma in the National Cancer Database between 2004 to 2016. Clinicopathologic factors, treatments, and outcomes were analyzed and compared between this cohort and adults (ages ≥20) with medullary thyroid carcinoma.
RESULTS
One hundred twenty-five pediatric medullary thyroid carcinoma (median age: 13) and 5,086 adult medullary thyroid carcinoma (median age: 57) patients were identified. Pediatric patients had smaller tumors (median diameter: 1.2 cm vs 2.0 cm; P < .001), lower rates of nodal metastases (n = 31, 36.9% vs 1,689, 50.4%; P = .02) but double the incidence of multifocal tumors (n = 70, 59.3%, vs 1,412, 29.9%; P < .001) compared with adults. Multifocal tumors conferred a significantly increased risk of nodal metastases in adult medullary thyroid carcinoma (64.4% vs 43.2%; P < .001) but not pediatric medullary thyroid carcinoma (37.7% vs 35.7%; P = .85). Nodal metastases were more frequent among older children (0-5 years: 0.0%, 6-12: 40.7%, 13-19: 41.7%; P = .04). However, rates of occult nodal metastases were similar between older children (6-19 years: n = 12, 21.4%) and adults (557, 25.8% P = .56).
CONCLUSION
Pediatric medullary thyroid carcinoma has lower rates of lymph node metastases compared with adults. The risk of nodal disease was low among the youngest children, but older children ages 6 to 19 were at considerable risk for occult metastases. These findings could guide clinicians in selecting pediatric patients considered for elective lymph node dissection.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Neuroendocrine; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Incidence; Infant; Infant, Newborn; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neck Dissection; Retrospective Studies; Thyroid Neoplasms; Thyroidectomy; United States; Young Adult
PubMed: 33838880
DOI: 10.1016/j.surg.2021.03.001 -
Medicina (Kaunas, Lithuania) Jun 2021: Medullary thyroid carcinoma (MTC) accounts for 1-2% of all thyroid malignancies, and it originates from parafollicular "C" cells. Carcinoembryonic antigen (CEA) is a... (Review)
Review
: Medullary thyroid carcinoma (MTC) accounts for 1-2% of all thyroid malignancies, and it originates from parafollicular "C" cells. Carcinoembryonic antigen (CEA) is a tumor marker, mainly for gastrointestinal malignancies. There are references in literature where elevated CEA levels may be the first finding in MTC. The aim of this study is to determine the importance of measuring preoperative and postoperative CEA values in patients with MTC and to define the clinical significance of the correlation between CEA and the origin of C cells. : The existing and relevant literature was reviewed by searching for articles and specific keywords in the scientific databases of PubMedCentraland Google Scholar (till December 2020). : CEA has found its place, especially at the preoperative level, in the diagnostic approach of MTC. Preoperative CEA values >30 ng/mL indicate extra-thyroid disease, while CEA values >100 ng/mL are associated with lymph node involvement and distant metastases. The increase in CEA values preoperatively is associated with larger size of primary tumor, presence of lymph nodes, distant metastases and a poorer prognosis. The clinical significance of CEA values for the surgeon is the optimal planning of surgical treatment. In the recent literature, C cells seem to originate from the endoderm of the primitive anterior gut at the ultimobranchial bodies' level. : Although CEA is not a specific biomarker of the disease in MTC, itsmeasurement is useful in assessing the progression of the disease. The embryonic origin of C cells could explain the increased CEA values in MTC.
Topics: Biomarkers, Tumor; Calcitonin; Carcinoembryonic Antigen; Carcinoma, Neuroendocrine; Humans; Thyroid Neoplasms
PubMed: 34208296
DOI: 10.3390/medicina57060609 -
Endokrynologia Polska 2014Thyroid nodular goitre is one of the most common endocrine disorders. Differentiating between benign and malignant lesions is an emerging challenge in endocrinological... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Thyroid nodular goitre is one of the most common endocrine disorders. Differentiating between benign and malignant lesions is an emerging challenge in endocrinological practice. Ultrasonography (US) remains the most commonly applied method in the preliminary assessment of lesions and is the basis for the decision as to fine needle aspiration biopsy (FNAB) and further diagnostics. Many studies have evaluated the diagnostic value of US malignancy features. However, they focused mainly on papillary thyroid cancer (PTC). It remains unclear whether other types of thyroid carcinoma (TC) are also characterised by the same US features. The aim of this study was to assess the usefulness of US features considered as markers in the diagnosis of medullary thyroid cancer (MTC).
MATERIAL AND METHODS
The PubMed/MEDLINE and Cochrane Library databases were searched to identify studies on US features of MTCs. The random-effects model was used to calculate pooled sensitivity and specificity and odds ratios (OR) - if a comparison with PTCs was available.
RESULTS
Hypoechogenicity was present in 83.4% of MTCs, and 32.7% were markedly hypoechogenic. None of the 157 MTCs was hyperechogenic. Sensitivity of halo absence was 88.9%, but irregular margins were present in 38.0%. 35.5% of MTCs had microcalcifications, and 27.0% had macrocalcifications. 14.4% presented 'taller than wide feature' (higher anteroposterior than transverse diameter). Apart from macrocalcifications, all these features occurred insignificantly less often in MTCs than in PTCs.
CONCLUSIONS
US features commonly considered as markers of malignancy can be useful also in the diagnostics of MTCs. However, MTCs tend to possess suspicious US features slightly less often than PTCs. Some features, such as hyperechogenicity, can be considered to be strong markers of benign status. Although the US appearance of the thyroid lesion is an important diagnostic factor, it is worth remembering that it does not allow for a definitive differentiation between benign and malignant nodules. In the case of MTCs, as well as other TCs, US examination remains a valuable diagnostic tool, but should always be interpreted carefully in the context of other examinations.
Topics: Calcinosis; Carcinoma, Medullary; Diagnosis, Differential; Humans; Predictive Value of Tests; Thyroid Diseases; Thyroid Neoplasms; Thyroid Nodule; Ultrasonography, Interventional
PubMed: 25185855
DOI: 10.5603/EP.2014.0043 -
Thyroid : Official Journal of the... Mar 2019Survival of medullary thyroid carcinoma (MTC) subgroups in relation to the general population is poorly described. Data on the factors predicting long-term biochemical...
BACKGROUND
Survival of medullary thyroid carcinoma (MTC) subgroups in relation to the general population is poorly described. Data on the factors predicting long-term biochemical cure in MTC patients are nonexistent at a population level. A nationwide retrospective cohort study of MTC in Denmark from 1997 to 2014 was conducted, aiming to detect subgroups with survival similar to that of the general population and to identify prognostic factors for disease-specific survival and long-term biochemical cure.
METHODS
The study included 220 patients identified from the nationwide Danish MTC cohort between 1997 and 2014. As a representative sample of the general population, a reference population matched 50:1 to the MTC cohort was used.
RESULTS
Patients diagnosed with hereditary MTC by screening (hazard ratio [HR] = 1.5 [confidence interval (CI) 0.5-4.3]), patients without regional metastases (HR = 1.4 [CI 0.9-2.3]), and patients with stage I (HR = 1.3 [CI 0.6-3.1]), stage II (HR = 1.1 [CI 0.6-2.3]), and III (HR = 1.3 [CI 0.4-4.2]) disease had an overall survival similar to the reference population. On multivariate analysis, the presence of distant metastases (HR = 12.3 [CI 6.0-25.0]) predicted worse disease-specific survival, while the absence of regional lymph node metastases (odds ratio = 40.1 [CI 12.0-133.7]) was the only independent prognostic factor for long-term biochemical cure.
CONCLUSIONS
Patients with hereditary MTC diagnosed by screening, patients without regional metastases, and patients with stages I, II, and III disease may have similar survival as the general population. The presence of distant metastases predicted worse disease-specific survival, while the absence of regional metastases predicted long-term biochemical cure.
Topics: Adult; Aged; Carcinoma, Medullary; Databases, Factual; Denmark; Disease-Free Survival; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Multiple Endocrine Neoplasia Type 2a; Prognosis; Proportional Hazards Models; Retrospective Studies; Thyroid Neoplasms; Treatment Outcome; Young Adult
PubMed: 30618340
DOI: 10.1089/thy.2018.0564 -
Cancer Biology & Therapy Jul 2017Although the FDA-approved receptor tyrosine kinases inhibitors, vandetanib and cabozantinib, are used to treat surgically inoperable progressive medullary thyroid...
Although the FDA-approved receptor tyrosine kinases inhibitors, vandetanib and cabozantinib, are used to treat surgically inoperable progressive medullary thyroid carcinoma (MTC), not all patients are responsive while the disease sometimes progresses after an initial response. To better understand MTC drug resistance at molecular and biochemical levels, we have generated drug-resistant subpopulations of the human MTC cell lines, TT and MZ-CRC-1, via prolonged exposure to vandetanib and cabozantinib. These drug-resistant progenies exhibited substantial cross-resistance to vandetanib and cabozantinib, suggesting that these inhibitors may invoke an overlapping resistance mechanism(s) in MTC cells. Of note, vandetanib and cabozantinib increased mitochondrial membrane potential (Δψ) in drug-naïve as well as drug-resistant cells but only drug-naïve cells exhibited substantially altered oxygen consumption and extracellular acidification rates. Therefore, these inhibitors appear to cause a bioenergetics stress to which drug-resistant MTC cells are more tolerant. Given the ability of vandetanib and cabozantinib to increase Δψ, we hypothesized that these inhibitors can augment growth inhibitory effects of mitochondria-targeted carboxy-proxyl and ubiquinone by increasing their Δψ-dependent uptake/retention in MTC cells. Indeed, our in vitro and mouse xenograft data strongly support this possibility.
Topics: Anilides; Animals; Carcinoma, Neuroendocrine; Cell Cycle; Cell Line, Tumor; Cell Survival; Disease Models, Animal; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Membrane Potential, Mitochondrial; Mice; Mitochondria; Mitochondrial Dynamics; Piperidines; Protein Kinase Inhibitors; Pyridines; Quinazolines; Thyroid Neoplasms; Xenograft Model Antitumor Assays
PubMed: 28475408
DOI: 10.1080/15384047.2017.1323594 -
Ear, Nose, & Throat Journal Jul 2010
Topics: Biopsy; Brain Stem Neoplasms; Calcitonin; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Humans; Thyroid Neoplasms
PubMed: 20628986
DOI: 10.1177/014556131008900712 -
BMC Endocrine Disorders Oct 2019Medullary thyroid carcinoma is a malignant uncommon and aggressive tumour of the parafollicular C cells. In about 75% of cases it is sporadic while, in case of RET... (Review)
Review
BACKGROUND
Medullary thyroid carcinoma is a malignant uncommon and aggressive tumour of the parafollicular C cells. In about 75% of cases it is sporadic while, in case of RET mutation, it is associated to multiple endocrine neoplasia type 2 (25% of cases). The biochemical features of medullary thyroid carcinoma include the production of calcitonin and carcinoembryogenic antigen. The above-mentioned features are useful in the diagnostic process as well as in the follow up and in the prognostication of the disease. Even if calcitonin elevation is strongly associated to MTC, it can also be found increased in many pathological different conditions as pregnancy, lactation, C-cells hyperplasia, autoimmune thyroiditis, end stage renal disease, lung and prostate cancer and several neuroendocrine tumours. Major medullary thyroid tumours are usually connected to high doses of circulating calcitonin, in fact non-secretory variants have hardly been described.
CASE PRESENTATION
We herein report the case of a 59 years old male, who had undergone total thyroidectomy for multinodular goiter with negative preoperative calcitonin, showing medullary thyroid carcinoma at definitive pathology. To the best of our knowledge, this is the first case documenting a non-secretory medullary thyroid carcinoma, with double negative markers at the time of diagnosis and at the relapse.
CONCLUSION
A Literature review underlining pathological hypothesis, differential diagnosis and alternative and innovative biomarkers to identify non-secretory medullary thyroid carcinoma was carried out.
Topics: Biomarkers, Tumor; Calcitonin; Carcinoembryonic Antigen; Carcinoma, Neuroendocrine; Diagnosis, Differential; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Thyroid Neoplasms; Thyroidectomy
PubMed: 31619220
DOI: 10.1186/s12902-019-0435-7