Medullary thyroid cancer in a 9-week-old infant with familial MEN 2B: Implications for timing of prophylactic thyroidectomy

Abstract

BackgroundPatients with Multiple Endocrine Neoplasia type 2 (MEN 2) are at high risk of developing aggressive medullary thyroid carcinoma (MTC) in childhood, with the highest risk in those with MEN type 2B (of whom >95% have an M918T RET proto-oncogene mutation). Metastatic MTC has been reported as young as 3 months of age. Current guidelines recommend prophylactic thyroidectomy within the first year of life for MEN 2B.Patient findingsWe report a 9-week-old infant with MTC due to familial MEN 2B. A full-term male infant, born to a mother with known MEN 2B and metastatic MTC, had an M918T RET proto-oncogene mutation confirmed at 4 weeks of age. He underwent prophylactic total thyroidectomy at 9 weeks of age. Pathology showed a focal calcitonin-positive nodule (2.5 mm), consistent with microscopic MTC.SummaryThis case highlights the importance of early prophylactic thyroidectomy in MEN 2B. Although current guidelines recommend surgery up to a year of life, MTC may occur in the first few weeks of life, raising the question of how early we should intervene. In this report, we discuss the risks, benefits and barriers to performing earlier thyroidectomy, soon after the first month of life, and make suggestions to facilitate timely intervention. Prenatal anticipatory surgical scheduling could be considered in familial MEN 2B. Multidisciplinary collaboration between adult and pediatric specialists is key to the optimal management of the infant at risk.

On the Origin of Cells and Derivation of Thyroid Cancer: C Cell Story Revisited

“…Germline activating RET mutations implies that mutant RET receptors are constitutively activated once being naturally expressed, which for C cells probably occur at the progenitor stage in pharyngeal endoderm or in precursor cells present in the ultimobranchial epithelium. In line with this assumption, germline RET 918 mutation may cause metastatic MTC with clinical manifestations already in infancy [70]. For germline mutations associated with a less aggressive MTC than 918 it is conceivable that RET is activated in the same developmental stage.…”

“…Cancer is often diagnosed in the teens or twenties in MEN2b and rarely at this young age in MEN2a. Notably, the youngest reported case in MEN2b was in a 9-week-old infant [70], and a case seen by one author was found at autopsy in a 6-week-old child. These findings suggest that the further mutations needed for carcinogenesis may in some cases occur during foetal life.…”

Cystic ovarian teratoma as a novel tumor and growth hormone deficiency as a new condition presenting in Multiple Endocrine Neoplasia type 2B: Case reports and review of the literature

“…The problem is that most of MEN2B patients carry de novo mutations. Shankar et al highlights prophylactic thyroidectomy in 9 weeks old infant with familial MEN2B in whom microscopic MTC has been already revealed 19 . An international, multicentre, retrospective study including 338 patients with MEN2B confirmed a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year 20 .…”