Abstract：
BACKGROUND: Sporadic medullary thyroid carcinoma (sMTC) rarely occurs in childhood and no studies have specifically focused on this entity.
OBJECTIVE: To describe the clinical presentations and long-term outcomes of a large cohort of children and young adults with sMTC compared with hereditary MTC (hMTC).
METHODS: Retrospective study of 144 patients diagnosed with MTC between 1961 and 2019 at an age ≤ 21 years and evaluated at a tertiary referral center.
RESULTS: In contrast to hMTC (n = 124/144, 86%), patients with sMTC (n = 20/144, 14%) are older (P < .0001), have larger tumors (P < .0001), a higher initial stage grouping (P = .001) and have more structural disease (P = .0045) and distant metastases (DM) (P = .00084) at last follow-up, but are not more likely to die from MTC (P = .42). Among 77 patients diagnosed clinically, not by family history (20/20 sMTC and 57/124 hMTC), there was no difference in the initial stage (P = .27), presence of DM at diagnosis (P = 1.0), disease status at last follow-up (P = .13), overall survival (P = .57), or disease-specific survival (P = .87). Of the 12 sMTC tumors that underwent somatic testing, 11 (91%) had an identifiable alteration: 10 RET gene alterations and 1 ALK fusion.
CONCLUSIONS: sMTC is primarily a RET-driven disease that represents 14% of childhood-onset MTC in this cohort. Pediatric sMTC patients are older, present with clinical disease at a more advanced TNM classification, and have more persistent disease at last follow-up compared with hMTC, but these differences disappear when comparing those presenting clinically. Somatic molecular testing should be considered in sMTC patients who would benefit from systemic therapy.
OBJECTIVE: To describe the clinical presentations and long-term outcomes of a large cohort of children and young adults with sMTC compared with hereditary MTC (hMTC).
METHODS: Retrospective study of 144 patients diagnosed with MTC between 1961 and 2019 at an age ≤ 21 years and evaluated at a tertiary referral center.
RESULTS: In contrast to hMTC (n = 124/144, 86%), patients with sMTC (n = 20/144, 14%) are older (P < .0001), have larger tumors (P < .0001), a higher initial stage grouping (P = .001) and have more structural disease (P = .0045) and distant metastases (DM) (P = .00084) at last follow-up, but are not more likely to die from MTC (P = .42). Among 77 patients diagnosed clinically, not by family history (20/20 sMTC and 57/124 hMTC), there was no difference in the initial stage (P = .27), presence of DM at diagnosis (P = 1.0), disease status at last follow-up (P = .13), overall survival (P = .57), or disease-specific survival (P = .87). Of the 12 sMTC tumors that underwent somatic testing, 11 (91%) had an identifiable alteration: 10 RET gene alterations and 1 ALK fusion.
CONCLUSIONS: sMTC is primarily a RET-driven disease that represents 14% of childhood-onset MTC in this cohort. Pediatric sMTC patients are older, present with clinical disease at a more advanced TNM classification, and have more persistent disease at last follow-up compared with hMTC, but these differences disappear when comparing those presenting clinically. Somatic molecular testing should be considered in sMTC patients who would benefit from systemic therapy.
摘要：
背景：散发性甲状腺髓样癌（sMTC）很少发生在儿童时期，并且没有研究专门针对该实体。
目的：描述与遗传性MTC（hMTC）相比，大量儿童和年轻人sMTC的临床表现和长期结局。
方法：对1961-2019年间诊断为MTC且年龄≤21岁的144例患者进行回顾性研究，并在三级转诊中心进行评估。
结果：与hMTC（n=124/144，86％）相反，sMTC患者（n=20/144，14%）年龄较大（p<0.0001），有较大的肿瘤（p<0.0001），较高的初始阶段分组（p=0.001）和更多的结构性疾病（p=0.0045）和远处转移（DM）（p=0.00084）在最后一次随访，但不会更容易死于MTC(p=0.42)。在临床诊断的77名患者中，不是家族史（20/20sMTC和57/124hMTC），在初始阶段没有差异(p=0.27)，诊断时存在DM（p=1.0），末次随访时的疾病状态（p=0.13），总生存率（p=0.57），或疾病特异性生存率（p=0.87）。在12个接受体细胞测试的sMTC肿瘤中，11个（91％）具有可识别的改变：10个RET基因改变和1个ALK融合。
结论：sMTC主要是RET驱动的疾病，在该队列中占儿童发作MTC的14%。儿科sMTC患者年龄较大，以更先进的TNM分类呈现临床疾病，与hMTC相比，在最后一次随访中有更多的持续性疾病，但是当比较临床上出现的差异时，这些差异消失了。应考虑将从全身治疗中受益的sMTC患者进行体细胞分子检测。
目的：描述与遗传性MTC（hMTC）相比，大量儿童和年轻人sMTC的临床表现和长期结局。
方法：对1961-2019年间诊断为MTC且年龄≤21岁的144例患者进行回顾性研究，并在三级转诊中心进行评估。
结果：与hMTC（n=124/144，86％）相反，sMTC患者（n=20/144，14%）年龄较大（p<0.0001），有较大的肿瘤（p<0.0001），较高的初始阶段分组（p=0.001）和更多的结构性疾病（p=0.0045）和远处转移（DM）（p=0.00084）在最后一次随访，但不会更容易死于MTC(p=0.42)。在临床诊断的77名患者中，不是家族史（20/20sMTC和57/124hMTC），在初始阶段没有差异(p=0.27)，诊断时存在DM（p=1.0），末次随访时的疾病状态（p=0.13），总生存率（p=0.57），或疾病特异性生存率（p=0.87）。在12个接受体细胞测试的sMTC肿瘤中，11个（91％）具有可识别的改变：10个RET基因改变和1个ALK融合。
结论：sMTC主要是RET驱动的疾病，在该队列中占儿童发作MTC的14%。儿科sMTC患者年龄较大，以更先进的TNM分类呈现临床疾病，与hMTC相比，在最后一次随访中有更多的持续性疾病，但是当比较临床上出现的差异时，这些差异消失了。应考虑将从全身治疗中受益的sMTC患者进行体细胞分子检测。
