BACKGROUND: Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. METHODS: This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features. FINDINGS: 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0·35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs. INTERPRETATION: Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year. FUNDING: None.
- MeSH
- dítě MeSH
- dospělí MeSH
- feochromocytom mortalita patologie chirurgie MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mezinárodní agentury MeSH
- míra přežití MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mnohočetná endokrinní neoplazie typ 2B mortalita patologie chirurgie MeSH
- nádory nadledvin mortalita patologie chirurgie MeSH
- nádory štítné žlázy mortalita patologie chirurgie MeSH
- následné studie MeSH
- neuroendokrinní karcinom mortalita patologie chirurgie MeSH
- předškolní dítě MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- tyreoidektomie mortalita MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- MeSH
- dospělí MeSH
- invazivní růst nádoru patologie MeSH
- Kaplanův-Meierův odhad MeSH
- karcinom * chirurgie mortalita patologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru * mortalita patologie MeSH
- lymfatické metastázy MeSH
- lymfatické uzliny * patologie MeSH
- míra přežití MeSH
- multivariační analýza MeSH
- nádory štítné žlázy * chirurgie mortalita patologie MeSH
- papilární karcinom štítné žlázy MeSH
- papilární karcinom * chirurgie mortalita patologie MeSH
- přežití po terapii bez příznaků nemoci MeSH
- prognóza MeSH
- program SEER MeSH
- proporcionální rizikové modely MeSH
- staging nádorů MeSH
- tyreoidektomie * metody mortalita MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- komentáře MeSH
- souhrny MeSH
Context: Multifocality is often treated as a risk factor for papillary thyroid cancer (PTC), prompting aggressive treatments, but its prognostic value remains unestablished. Objective: To investigate the role of tumor multifocality in clinical outcomes of PTC. Methods: Multicenter study of the relationship between multifocality and clinical outcomes of PTC in 2638 patients (623 men and 2015 women) with median [interquartile range (IQR)] age of 46 (35 to 58) years and median (IQR) follow-up time of 58 (26 to 107) months at 11 medical centers in six countries. Surveillance, Epidemiology and End Results (SEER) data were used for validation. Results: Disease recurrence in multifocal and unifocal PTC was 198 of 1000 (19.8%) and 221 of 1624 (13.6%) (P < 0.001), with a hazard ratio of 1.55 [95% confidence interval (CI), 1.28 to 1.88], which became insignificant at 1.13 (95% CI, 0.93 to 1.37) on multivariate adjustment. Similar results were obtained in PTC variants: conventional PTC, follicular-variant PTC, tall-cell PTC, and papillary thyroid microcarcinoma. There was no association between multifocality and mortality in any of these PTC settings, whereas there was a strong association between classic risk factors and cancer recurrence or mortality, which remained significant after multivariate adjustment. In 1423 patients with intrathyroidal PTC, disease recurrence was 20 of 455 (4.4%) and 41 of 967 (4.2%) (P = 0.892) and mortality was 0 of 455 (0.0%) and 3 of 967 (0.3%) (P = 0.556) in multifocal and unifocal PTC, respectively. The results were reproduced in 89,680 patients with PTC in the SEER database. Conclusions: Tumor multifocality has no independent risk prognostic value in clinical outcomes of PTC; its indiscriminate use as an independent risk factor, prompting overtreatments of patients, should be avoided.
- MeSH
- dospělí MeSH
- invazivní růst nádoru patologie MeSH
- Kaplanův-Meierův odhad MeSH
- karcinom mortalita patologie chirurgie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru mortalita patologie MeSH
- lymfatické metastázy MeSH
- lymfatické uzliny patologie MeSH
- míra přežití MeSH
- multivariační analýza MeSH
- nádory štítné žlázy mortalita patologie chirurgie MeSH
- papilární karcinom mortalita patologie chirurgie MeSH
- přežití po terapii bez příznaků nemoci MeSH
- prognóza MeSH
- program SEER MeSH
- proporcionální rizikové modely MeSH
- staging nádorů MeSH
- tyreoidektomie metody mortalita MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- srovnávací studie MeSH
