Unusual presentation of medullary thyroid carcinoma: Regional and distant metastases in the background of benign non-neoplastic Multi-Nodular Goiter

Background and Objectives: 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. Materials and Methods: 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). Results: 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. Conclusions: 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.

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Medullary thyroid carcinoma: recent advances in identification, treatment, and prognosis

Therapeutic Advances in Endocrinology and Metabolism ◽

10.1177/20420188211049611 ◽

2021 ◽

Vol 12 ◽

pp. 204201882110496

Author(s):

Marisa A. Bartz-Kurycki ◽

Omowunmi E. Oluwo ◽

Lilah F. Morris-Wiseman

Keyword(s):

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Distant Metastases ◽

Hereditary Disease ◽

Patient Specific ◽

Medullary Thyroid ◽

Recent Advances ◽

Initial Surgery ◽

Biochemical Testing ◽

Thyroid Malignancies

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor that represents <5% of all thyroid malignancies and is generally more aggressive than differentiated thyroid cancer. The aim of this study is to provide an update, through review of clinical studies of patients with MTC published between January 1, 2016, and June 1, 2021, on recent advances in the diagnosis and treatment of MTC. This review focuses on updates in biochemical testing, imaging, hereditary disease, surgical management, adjuvant therapies, and prognosis. Recent advances reviewed herein have sought to diagnose MTC at earlier stages of disease, predict when patients with a hereditary syndrome may develop MTC, use functional imaging to assess for distant metastases, perform optimal initial surgery with appropriate lymphadenectomy, employ targeted systemic therapies for patients with progressive metastatic disease, and better predict patient-specific outcomes.

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Polymorphisms of cell cycle control genes influence the development of sporadic medullary thyroid carcinoma

Acta Endocrinologica ◽

10.1530/eje-14-0461 ◽

2014 ◽

Vol 171 (6) ◽

pp. 761-767 ◽

Cited By ~ 12

Author(s):

R B Barbieri ◽

N E Bufalo ◽

R Secolin ◽

L V M Assumpção ◽

R M B Maciel ◽

...

Keyword(s):

Cell Cycle ◽

Regression Analysis ◽

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Cell Cycle Control ◽

Multivariate Logistic Regression Analysis ◽

Distant Metastases ◽

Genetic Profile ◽

Sporadic Medullary Thyroid Carcinoma ◽

Medullary Thyroid

BackgroundThe role of key cell cycle regulation genes such as, CDKN1B, CDKN2A, CDKN2B, and CDKN2C in sporadic medullary thyroid carcinoma (s-MTC) is still largely unknown.MethodsIn order to evaluate the influence of inherited polymorphisms of these genes on the pathogenesis of s-MTC, we used TaqMan SNP genotyping to examine 45 s-MTC patients carefully matched with 98 controls.ResultsA multivariate logistic regression analysis demonstrated that CDKN1B and CDKN2A genes were related to s-MTC susceptibility. The rs2066827*GT+GG CDKN1B genotype was more frequent in s-MTC patients (62.22%) than in controls (40.21%), increasing the susceptibility to s-MTC (OR=2.47; 95% CI=1.048–5.833; P=0.038). By contrast, the rs11515*CG+GG of CDKN2A gene was more frequent in the controls (32.65%) than in patients (15.56%), reducing the risk for s-MTC (OR=0.174; 95% CI=0.048–0.627; P=0.0075). A stepwise regression analysis indicated that two genotypes together could explain 11% of the total s-MTC risk. In addition, a relationship was found between disease progression and the presence of alterations in the CDKN1A (rs1801270), CDKN2C (rs12885), and CDKN2B (rs1063192) genes. WT rs1801270 CDKN1A patients presented extrathyroidal tumor extension more frequently (92%) than polymorphic CDKN1A rs1801270 patients (50%; P=0.0376). Patients with the WT CDKN2C gene (rs12885) presented larger tumors (2.9±1.8 cm) than polymorphic patients (1.5±0.7 cm; P=0.0324). On the other hand, patients with the polymorphic CDKN2B gene (rs1063192) presented distant metastases (36.3%; P=0.0261).ConclusionIn summary, we demonstrated that CDKN1B and CDKN2A genes are associated with susceptibility, whereas the inherited genetic profile of CDKN1A, CDKN2B, and CDKN2C is associated with aggressive features of tumors. This study suggests that profiling cell cycle genes may help define the risk and characterize s-MTC aggressiveness.

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Medullary Thyroid Carcinoma with Micronodular Lung Metastases: A Case Report with an Emphasis on the Imaging Findings

Case Reports in Medicine ◽

10.1155/2010/616580 ◽

2010 ◽

Vol 2010 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Nina Ventura ◽

Edson Marchiori ◽

Gláucia Zanetti ◽

Antonio Muccillo ◽

Mariana Leite Pereira ◽

...

Keyword(s):

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Medullary Thyroid Cancer ◽

Lung Metastases ◽

Disease Process ◽

Distant Metastases ◽

Diagnostic Tools ◽

Case Discussion ◽

Medullary Thyroid ◽

Rare Malignancy

Medullary thyroid carcinoma is a rare malignancy that arises from calcitonin-producing C-cells and frequently metastasizes to lymph nodes in the neck. Distant metastases may involve bone, lung, and liver. The infrequent number of cases limits the clinical nature and ability to optimize diagnostic tools. Here, we present a case of a micronodular radiographic pattern in metastatic medullary thyroid cancer in order to enhance awareness of the disease process. A case discussion and relevant review of the literature are provided.

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Radioactive iodine in the treatment of medullary thyroid carcinoma: a controlled multicenter study

Acta Endocrinologica ◽

10.1530/eje-12-0943 ◽

2013 ◽

Vol 168 (5) ◽

pp. 779-786 ◽

Cited By ~ 15

Author(s):

J A A Meijer ◽

L E H Bakker ◽

G D Valk ◽

W W de Herder ◽

J H W de Wilt ◽

...

Keyword(s):

Multivariate Analysis ◽

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Multicenter Study ◽

Radioactive Iodine ◽

Disease Free Survival ◽

Distant Metastases ◽

Medullary Thyroid ◽

Clinical Appearance ◽

Significant Difference

ObjectiveRadioactive iodine (RAI) therapy in medullary thyroid carcinoma (MTC) is applied in some centers, based on the assumption that cross-irradiation from thyroid follicular cells may be beneficial. However, no systematic studies on the effect of RAI treatment in MTC have been performed. The aim of this study was to analyze the effect of RAI treatment on survival in MTC patients.DesignRetrospective multicenter study in eight University Medical Centers in The Netherlands.MethodsTwo hundred and ninety three MTC patients without distant metastases who had undergone a total thyroidectomy were included between 1980 and 2007. Patients were stratified by clinical appearance, hereditary stage, screening status, and localization. All patients underwent regular surgical treatment with additional RAI treatment in 61 patients. Main outcome measures were disease-free survival (DFS) and disease-specific survival (DSS). Cure was defined as biochemical and radiological absence of disease.ResultsIn multivariate analysis, stratification according to clinical appearance (P=0.72), hereditary stage (P=0.96), localization (P=0.69), and screening status (P=0.31) revealed no significant effects of RAI treatment on DFS. Multivariate analysis showed no significant difference in DSS for the two groups stratified according to clinical appearance (P=0.14). Owing to limited number of events, multivariate analysis was not possible for DSS in the other groups of stratification.ConclusionsBased on the results of the present analysis, we conclude that RAI has no place in the treatment of MTC.

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An Unusual Presentation of Medullary Thyroid Carcinoma

Indian Journal of Otolaryngology and Head & Neck Surgery ◽

10.1007/s12070-013-0624-z ◽

2013 ◽

Vol 65 (S1) ◽

pp. 195-198 ◽

Cited By ~ 3

Author(s):

Sudip Kr Das ◽

Himanshu Varshney ◽

M. L. Saha ◽

Shubhrakanti Sen ◽

Amit Bikram Maity ◽

...

Keyword(s):

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Unusual Presentation ◽

Medullary Thyroid

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Calcitonin doubling time in medullary thyroid carcinoma after the detection of distant metastases keenly predicts patients’ carcinoma death

Endocrine Journal ◽

10.1507/endocrj.ej16-0140 ◽

2016 ◽

Vol 63 (7) ◽

pp. 663-667 ◽

Cited By ~ 7

Author(s):

Yasuhiro Ito ◽

Akira Miyauchi ◽

Minoru Kihara ◽

Takumi Kudo ◽

Akihiro Miya

Keyword(s):

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Doubling Time ◽

Distant Metastases ◽

Medullary Thyroid

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Calcitonin Measurement to Detect Medullary Thyroid Carcinoma in Nodular Goiter: German Evidence-Based Consensus Recommendation

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2004-815727 ◽

2004 ◽

Vol 112 (01) ◽

pp. 52-58 ◽

Cited By ~ 85

Author(s):

W. Karges ◽

H. Dralle ◽

F. Raue ◽

K. Mann ◽

C. Reiners ◽

...

Keyword(s):

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Nodular Goiter ◽

Evidence Based ◽

Consensus Recommendation ◽

Medullary Thyroid

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The RET polymorphic allele S836S is associated with early metastatic disease in patients with hereditary or sporadic medullary thyroid carcinoma

Endocrine Related Cancer ◽

10.1677/erc-09-0312 ◽

2010 ◽

Vol 17 (4) ◽

pp. 953-963 ◽

Cited By ~ 25

Author(s):

Débora R Siqueira ◽

Mírian Romitti ◽

Andreia P da Rocha ◽

Lucieli Ceolin ◽

Camila Meotti ◽

...

Keyword(s):

Lymph Node ◽

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Metastatic Disease ◽

Cox Regression ◽

Distant Metastases ◽

Medullary Thyroid ◽

Kaplan Meier ◽

Increased Risk

The possible role of RET variants in modifying the natural course of medullary thyroid carcinoma (MTC) is still a matter of debate. Here, we investigate whether the RET variants L769L, S836S, and G691S/S904S influence disease presentation in hereditary or sporadic MTC patients. One hundred and two patients with hereditary MTC and 81 patients with sporadic MTC attending our institution were evaluated. The frequencies of RET polymorphisms in hereditary MTC were as follows: L769L, 17.3%; S836S, 7.95%; and S904S/G691S, 18.2%. No associations were observed between these polymorphisms and pheochromocytoma, hyperparathyroidism, lymph node, or distant metastasis. However, patients harboring the S836S variant were younger than those without this allele (17±8.2 vs 28.6±14.4 years, P=0.01), suggesting that these patients had metastases at a young age. Accordingly, the cumulative frequency of local and/or distant metastases as estimated by Kaplan–Meier curves showed that lymph node and distant metastases occurred earlier in patients harboring the S836S variant (P=0.003 and P=0.026 respectively). The S836S allele frequency was higher in sporadic MTC patients than in controls (10.5 vs 3.1%, P=0.01). Individuals harboring the S836S variant were younger (38.6±13.3 vs 48.5±16.7 years, P=0.02) and showed a higher percentage of lymph node and distant metastases (P=0.02 and P=0.04 respectively). Kaplan–Meier estimates of lymph node and distant metastases yielded distinct curves for patients with or without the S836S allele (P=0.002 and P=0.001 respectively). Additional analyses using a COX regression model showed that the S836S variant was independently associated with metastatic disease (hazard ratio 2.82 (95% confidence interval 1.51–5.26), P=0.001). In conclusion, the RET S836S variant is associated with early onset and increased risk for metastatic disease in patients with hereditary or sporadic MTC.

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