Analysis of risk factors for cervical lymph node metastases in patients with sporadic medullary thyroid carcinoma

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Abstract

Objective

Medullary thyroid carcinoma (MTC) is classified as either sporadic or inherited. This study was performed to analyze the risk factors for cervical lymph node metastases and predict the indication for prophylactic lateral neck dissection in patients with sporadic MTC.

Methods

Sixty-five patients with sporadic MTC were retrospectively reviewed. Univariate analysis with the chi-square test and multiple logistic regression analysis were applied to identify the clinicopathological features (sex, age, tumor size, number of tumor foci, capsule or vascular invasion, and others) associated with cervical lymph node metastases.

Results

The metastasis rates in the central and lateral compartments were 46.2% (30/65) and 40.0% (26/65), respectively. The incidence of cervical lymph node metastases was significantly higher in patients with a tumor size of >1 cm, tumor multifocality, and thyroid capsule invasion. Only thyroid capsule invasion was an independent predictive factor for central compartment metastases and lateral neck metastases. The possibility of central compartment metastases was significantly higher when the preoperative serum carcinoembryonic antigen concentration was >30 ng/mL (60.0% vs. 34.3%).

Conclusions

MTC is associated with a high incidence of cervical lymph node metastases. Prophylactic lateral node dissection is necessary in patients with thyroid capsule invasion or a high serum carcinoembryonic antigen concentration.

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Most cited references 19

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Biomarker-based risk stratification for previously untreated medullary thyroid cancer.

Henning Dralle, Andreas Machens (2010)

Preoperative neck ultrasonography may yield false-negative findings in more than one-third of medullary thyroid cancer (MTC) patients. If not cleared promptly, cervical lymph node metastases may emerge subsequently. Reoperations entail an excess risk of surgical morbidity and may be avoidable. This comprehensive investigation aimed to evaluate in a head-to-head comparison the clinical utility of pretherapeutic biomarker serum levels (basal calcitonin; stimulated calcitonin; carcinoembryonic antigen) for indicating extent of disease and providing biochemical stratification of pretherapeutic MTC risk. This was a retrospective analysis. The setting was a tertiary referral center. Included were 300 consecutive patients with previously untreated MTC. The intervention was compartment-oriented surgery. Stratified biomarker levels were correlated with histopathologic extent of disease. Higher biomarker levels reflected larger primary tumors and more lymph node metastases. Stratified basal calcitonin serum levels correlated better (r = 0.59) with the number of lymph node metastases than carcinoembryonic antigen (r = 0.47) or pentagastrin-stimulated calcitonin (r = 0.40) levels. Lymph node metastases were present in the ipsilateral central and lateral neck, contralateral central neck, contralateral lateral neck, and upper mediastinum, respectively, beyond basal calcitonin thresholds of 20, 50, 200, and 500 pg/ml. Bilateral compartment-oriented neck surgery achieved biochemical cure in at least half the patients with pretherapeutic basal calcitonin levels of 1,000 pg/ml or less but not in patients with levels greater than 10,000 pg/ml. Most newly diagnosed MTC patients, i.e. those with pretherapeutic basal calcitonin levels greater than 200 pg/ml, may need bilateral compartment-oriented neck surgery to reduce the number of reoperations.

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Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems.

E Kebebew, Daniel Clark, Quan-Yang Duh … (2000)

The clinical courses of patients with medullary thyroid carcinoma (MTC) vary, and a number of prognostic factors have been studied, but the significance of some of these factors remains controversial. The study group consisted of 104 patients with MTC or C-cell hyperplasia managed at the hospitals of the University of California, San Francisco, between January 1960 and December 1998. Patients were classified as having sporadic MTC, familial non-multiple endocrine neoplasia (MEN) MTC, MEN 2A, or MEN 2B. The TNM, European Organization for Research and Treatment of Cancer (EORTC), National Thyroid Cancer Treatment Cooperative Study (NTCTCS), and Surveillance, Epidemiology, and End Results (SEER) extent-of-disease stages were determined for each patient. The predictive values of these staging or prognostic scoring systems were compared by calculating the proportion of variance explained (PVE) for each system. Fifty-six percent of the patients had sporadic MTC, 22% had familial MTC, 15% had MEN 2A, and 7% had MEN 2B. The overall average age at diagnosis was 38 years, and patients with sporadic MTC presented at an older age (P < 0.05). Thirty-two percent of the patients with hereditary MTC were diagnosed by screening (genetic and/or biochemical). These patients had a lower incidence of cervical lymph node metastasis (P < 0.05) and 94.7% were cured at last follow-up (P < 0.0001) compared with patients not screened. Patients with sporadic MTC who had systemic symptoms (diarrhea, bone pain, or flushing) had widely metastatic MTC and 33.3% of those patients died within 5 years. Overall, 49.4% of the patients were cured, 12.3% had recurrent MTC, and 38.3% had persistent MTC. The mean follow-up time was 8.6 years (median, 5.0 years) with 10.7% (n=11) and 13.5% (n=14) cause specific mortality at 5 and 10 years, respectively. Patients with persistent or recurrent MTC who died of MTC lived for an average of 3.6 years (ranging from 1 month to 23.7 years). Patients who had total or subtotal thyroidectomy were less likely to have persistent or recurrent MTC (P < 0.05), and patients who had total thyroidectomy with cervical lymph node clearance required fewer reoperations for persistent or recurrent MTC (P < 0.05) than patients who underwent lesser procedures. In univariate analysis, age, gender, clinical presentation, TNM stage, sporadic/hereditary MTC, distant metastasis, and extent of thyroidectomy were significant prognostic factors. Only age and stage, however, remained independent prognostic factors in multivariate analysis. The TNM, EORTC, NTCTCS, and SEER staging systems were all accurate predictors of survival, but the EORTC prognostic scoring system had the highest PVE in this cohort. Screening for MTC and early treatment (total thyroidectomy with central neck lymph node clearance) had nearly a 100% cure rate. Patients with postoperative hypercalcitoninemia without clinical or radiologic evidence of residual tumor after apparently curative surgery may enjoy long term survival but have occult MTC. Only patient age at presentation and TNM stage were independent predictors of survival. The EORTC criteria, which included the greatest number of significant prognostic factors in our cohort, had the highest predictive value. Copyright 2000 American Cancer Society.

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Early malignant progression of hereditary medullary thyroid cancer.

Andreas Machens, Josef Hoegel, … (2003)

An age-related progression from C-cell hyperplasia to medullary thyroid carcinoma is associated with various germ-line mutations in the rearranged during transfection (RET) proto-oncogene that could be used to identify the optimal time for prophylactic surgery. In this European multicenter study conducted from July 1993 to February 2001, we enrolled patients who had a RET point mutation in the germ line, were 20 years of age or younger, were asymptomatic, and had undergone total thyroidectomy after confirmation of the RET mutation. Exclusion criteria were medullary thyroid carcinomas of more than 10 mm in greatest dimension and distant metastasis. Altogether, 207 patients from 145 families were identified. There was a significant age-related progression from C-cell hyperplasia to medullary thyroid carcinoma and, ultimately, nodal metastasis in patients whose RET mutations were grouped according to the extracellular- and intracellular-domain codons affected and in those with the codon 634 genotype. No lymph-node metastases were noted in patients younger than 14 years of age. The age-related penetrance was unaffected by the type of amino acid substitution encoded by the various codon 634 mutations. The codon-specific differences in the age at presentation of cancer and the familial rates of concomitant adrenal and parathyroid involvement suggest that the risk of progression was based on the transforming potential of the individual RET mutation. These data provide initial guidelines for the timing of prophylactic thyroidectomy in asymptomatic carriers of RET gene mutations. Copyright 2003 Massachusetts Medical Society

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Author and article information

Journal

Journal ID (nlm-ta): J Int Med Res

Journal ID (iso-abbrev): J. Int. Med. Res

Journal ID (publisher-id): IMR

Journal ID (hwp): spimr

Title: The Journal of International Medical Research

Publisher: SAGE Publications (Sage UK: London, England )

ISSN (Print): 0300-0605

ISSN (Electronic): 1473-2300

Publication date (Electronic): 23 March 2018

Publication date (Print): May 2018

Volume: 46

Issue: 5

Pages: 1982-1989

Affiliations

[1 ]Department of Surgical Oncology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

[2 ]Department of Medical Oncology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

Author notes

[*]

These authors contributed equally to this work.

[*]Fusheng Wu, Department of Surgical Oncology, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, P.R. China. Email: wufusheng@ 123456zju.edu.cn

Author information

Weina Fan http://orcid.org/0000-0003-4683-6121

Article

Publisher ID: 10.1177_0300060518762684

DOI: 10.1177/0300060518762684

PMC ID: 5991226

PubMed ID: 29569965

SO-VID: f80a4245-4ee3-4699-9cb0-bb789ee41a06

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Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

Analysis of risk factors for cervical lymph node metastases in patients with sporadic medullary thyroid carcinoma

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Abstract

Objective

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Conclusions

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International Journal of Medicine and Medical Research

Most cited references 19

Biomarker-based risk stratification for previously untreated medullary thyroid cancer.

Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems.

Early malignant progression of hereditary medullary thyroid cancer.

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