Is new American Thyroid Association risk classification for hereditary medullary thyroid carcinoma applicable to Chinese patients? A single-center study

Abstract

ObjectiveThe American Thyroid Association (ATA) proposed a new risk classification for hereditary medullary thyroid carcinoma (MTC) in 2015. This study aimed to assess whether the new guidelines are suitable for the Chinese population, and reported our experience on prophylactic thyroidectomy.MethodsA total of 73 patients from 22 families were screened as rearranged during transfection (RET) mutation carriers from 2010 to 2016 in Cancer Hospital, Chinese Academy of Medical Science; the medical history for each patient was collected. Based on the initial treatment, we identified the risk factors for poor prognosis by univariate and multivariate logistic regression. Then, 4 RET mutation carriers were enrolled for prophylactic thyroidectomy, and their pathological data and follow-up outcomes were recorded. ResultsIn univariate and multivariate logistic regression analyses, age at initial surgery and risk classification were significant risk factors for stage III/IV hereditary MTC at initial diagnosis. The likelihood was increased by 11.6% per year of age at initial surgery [95% confidence interval (95% CI), 1.040–1.198; P=0.002). It was 7.888 times more likely to have III/IV stage disease for ATA highest risk patients, compared to ATA moderate risk individuals (95% CI, 1.607–38.717; P=0.003). Postoperative pathological results showed all 4 multiple endocrine neoplasia type 2A (MEN2A) patients had C-cell hyperplasia (CCH); multifocal malignancies were detected in 3 of them. All 4 patients were cured biochemically, and none developed permanent hypoparathyroidism.ConclusionsIn Chinese individuals, hereditary MTC aggressiveness is in line with the new ATA risk classification. Germline RET gene mutation carriers should undergo prophylactic thyroidectomy according to basal serum calcitonin levels.

GLOBAL ENDOCRINOLOGY: Geographical variation in the profile of RET variants in patients with medullary thyroid cancer: a comprehensive review

“…pathogenic variants from countries across five continents (excluding Brazil, Denmark, France, Germany, Italy, Japan, Norway, UK, and USA). Tyr606Cys, p.Cys618Tyr, p.Cys618Arg, p.Cys618Ser, p.Cys620Tyr, p.Leu790Phe, and p.Ser891Ala(97,98,99,100,101,102). Recently, there have been reports indicating the double pathogenic variants in the same patient, as in a large pedigree of 33 patients harboring p.Cys634/p.Asp707Glu, with a probably modifying effect in the age of onset and disease severity(103).…”

Hereditary Medullary Thyroid Carcinoma: Genotype, Phenotype and Outcomes in a North Indian Cohort

“…In this first comprehensive report on hMTC patients from India studying the genotype and phenotype, we found that the overall survival rates did not differ between the three ATA risk‐groups. This is in stark variance to the conventional notion that the RET genotype in hMTC correlates with the disease aggressiveness and outcomes [27, 28]. It seems prudent that the current ATA genotype based risk grouping system is relevant to those detected by the genetic screening.…”

Research progress on familial medullary thyroid cancer

“…Traditional concepts believe that the RET genotype of HMTC is closely related to the invasiveness of the disease. Further studies show that the high-risk group was significantly more aggressive than the medium-risk group, and patients with high-risk mutations had a significantly later clinical stage at initial diagnosis [32].…”