A comprehensive review on MEN2B

Abstract

MEN2B is a very rare autosomal dominant hereditary tumor syndrome associated with medullary thyroid carcinoma (MTC) in 100% cases, pheochromocytoma in 50% cases and multiple extra-endocrine features, many of which can be quite disabling. Only few data are available in the literature. The aim of this review is to try to give further insights into the natural history of the disease and to point out the missing evidence that would help clinicians optimize the management of such patients. MEN2B is mainly characterized by the early occurrence of MTC, which led the American Thyroid Association to recommend preventive thyroidectomy before the age of 1 year. However, as the majority of mutations are de novo, improved knowledge of the nonendocrine signs would help to lower the age of diagnosis and improve long-term outcomes. Future large-scale studies will be aimed at characterizing more in detail the main characteristics and outcomes of MEN2B.

Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study

“…Multiple endocrine neoplasia type 2B (MEN 2B) is a rare genetic syndrome (prevalence, 0.9-1.65 per million; incidence, 1.4-2.6 per million live births per year) caused by germline mutations of the protooncogene RET [1][2][3][4] . MEN 2B is most commonly caused by the p.M918T RET mutation (> 95% cases) followed by the p.A883F mutation (< 5% cases) [5][6][7] ; very rarely, MEN 2B results from tandem RET mutations 8 . Precise data on the phenotypic characteristics and natural history of patients carrying the most common p.M918T mutation remain scarce.…”

65 YEARS OF THE DOUBLE HELIX: Exploiting insights on the RET receptor for personalized cancer medicine

“…In rare cases, MEN2A patients may have other noncancerous phenotypes, such as cutaneous lichen amyloidosis (itchy hyperpigmented epidermal plaques) or increased incidence of the congenital gut abnormality Hirschsprung disease (Wells et al 2015). The clinically more severe MEN2B subtype has earlier disease onset and is also characterized by MTC and PCC but in addition, with developmental anomalies of several systems, including Marfanoid habitus, ganglioneuromas of the mouth and intestines and delayed puberty (Castinetti et al 2018). Over 90% of MEN2B presents as de novo cases, making timely diagnosis challenging (Brauckhoff et al 2014, Castinetti et al 2018.…”

“…The clinically more severe MEN2B subtype has earlier disease onset and is also characterized by MTC and PCC but in addition, with developmental anomalies of several systems, including Marfanoid habitus, ganglioneuromas of the mouth and intestines and delayed puberty (Castinetti et al 2018). Over 90% of MEN2B presents as de novo cases, making timely diagnosis challenging (Brauckhoff et al 2014, Castinetti et al 2018.…”

“…Further, MEN2B is clinically more aggressive, with earlier metastasis, narrowing the window where early thyroidectomy will provide effective cure (Brauckhoff et al 2014, Castinetti et al 2018. Thus, early recognition of nonendocrine signs of MEN2B, detailed earlier (Brauckhoff et al 2014, Castinetti et al 2018, by pediatricians, dentists and other health care providers is critical to minimizing delays in diagnosis and improving outcomes. Despite advances, surgical cure for MEN2B-MTC operated after age 4 years is rare (Brauckhoff et al 2014).…”

Long‐term follow‐up of RET Y791F carriers in Denmark 1994‐2017: A National Cohort Study

“…MEN2A is characterized by MTC in conjunction with a varying penetrance of pheochromocytoma, primary hyperparathyroidism, cutaneous lichen amyloidosis, and Hirschsprung's disease . MEN2B is characterized by early onset MTC, pheochromocytoma, mucosal neuromas, and a marfanoid habitus . With a respective incidence of 28.4 and 2.6 per million live births per year, MEN2A and MEN2B are rare diseases .…”