The clinical consequences of diagnostic delay in sporadic pediatric MEN2B: a case series of 6 children.

This study aimed to retrospectively analyze the clinical characteristics, tumor staging, surgical outcomes, and prognosis of children with MEN2B who presented with MTC. By summarizing our single-center experience, we emphasize the importance of early recognition and genetic screening to provide clinical insights for improving prognosis. Clinical data of six pediatric patients diagnosed with MEN2B in BCH, between January 2019 and December 2023, were reviewed. Demographic characteristics, clinical presentation, laboratory and imaging findings, genetic testing, surgical details, and follow-up information were analyzed. Descriptive statistical methods were used for data analysis. The cohort included 6 patients (2 males, 4 females) with a median age of 9.2 years (range 8.1-14.4 years). All patients harbored the de novo p.M918T RET mutation. All patients exhibited the classic MEN2B phenotype (marfanoid habitus, ocular signs, multiple oral mucosal neuromas, vocal cord nodules, high-arched palate, etc.) accompanied by alacrima and gastrointestinal symptoms. All underwent total thyroidectomy and bilateral central compartment neck dissection, with five undergoing concurrent lateral neck dissection due to suspected metastasis. Postoperative pathology confirmed MTC in all cases, with cervical lymph node metastases present in 4 patients (66.7%). Preoperative calcitonin levels were markedly elevated. After a median postoperative follow-up of 2.8 years (range 2.1 to 4.5 years), only one patient (T2N0M0) achieved biochemical remission. Children with MEN2B demonstrate a highly characteristic and complete phenotypic spectrum. However, diagnostic delay in children with sporadic MEN2B is common, often leading to lymph node metastasis at diagnosis. Enhancing awareness of its distinctive features among relevant specialists and establishing efficient multidisciplinary team-based recognition and referral pathways are crucial for achieving early genetic diagnosis, enabling timely prophylactic surgery, and ultimately improving long-term outcomes. • Sporadic MEN2B, typically caused by the RET p.M918T mutation, is highly aggressive and requires prophylactic thyroidectomy within the first year of life. • Diagnosis is often delayed due to low awareness of the syndrome, leading to advanced medullary thyroid carcinoma at presentation. • All six children in this series exhibited the complete MEN2B phenotype (marfanoid habitus, mucosal neuromas, alacrima, gastrointestinal symptoms) yet were diagnosed late, with 66.7% having lymph node metastases. • Despite radical surgery, only one patient achieved biochemical remission, highlighting that delayed diagnosis severely compromises prognosis.