Surgical Curability of Medullary Thyroid Cancer in Multiple Endocrine Neoplasia 2B
- 1 April 2014
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Annals of Surgery
- Vol. 259 (4), 800-806
- https://doi.org/10.1097/sla.0b013e3182a6f43a
Abstract
This investigation aimed at exploring the suitability of nonendocrine manifestations preceding medullary thyroid cancer (MTC) for early diagnosis of multiple endocrine neoplasia type 2B (MEN 2B). MEN 2B patients, running a high risk of metastatic MTC, must be diagnosed early for biochemical cure. Forty-four MEN 2B patients carrying inherited (3 patients) and de novo (41 patients) M918T RET mutations were examined for signs and symptoms prompting MEN 2B. All 3 patients with inherited mutations were diagnosed before the age of 1 year and cured of their C-cell disease. Among 41 patients with de novo mutations, MEN 2B was diagnosed in 12 patients after recognition of nonendocrine manifestations [intestinal ganglioneuromatosis (6 patients), oral symptoms (5 patients), ocular ("tearless crying") (4 patients), and skeletal stigmata (1 patient) alone or concomitantly]. In the remaining 29 patients with de novo mutations, the diagnosis of MEN 2B was triggered by symptomatic MTC (28 patients) or pheochromocytoma (1 patient). The former patients, being significantly (P < 0.001) younger (means of 5.3 vs 17.6 years) and having lower calcitonin levels (means of 115 vs 25,519 pg/mL), smaller tumors (67% vs 0% were ≤10 mm) and less often extrathyroidal extension (0% vs 81%), lymph node (42% vs 100%), and distant metastases (8% vs 79%), were biochemically cured more often (58% vs 0%). MTC is curable in patients with de novo mutations when nonendocrine MEN 2B components are quickly appreciated and surgical intervention is performed before patients turn 4 years old.Keywords
This publication has 35 references indexed in Scilit:
- Molecular epidemiology of multiple endocrine neoplasia 2: implications for RET screening in the new milleniumActa Endocrinologica, 2013
- Multiple endocrine neoplasia type 2 syndromes (MEN 2): results from the ItaMEN network analysis on the prevalence of different genotypes and phenotypesActa Endocrinologica, 2010
- Medullary Thyroid Cancer: Management Guidelines of the American Thyroid AssociationThyroid®, 2009
- Medullary thyroid carcinoma identified within the first year of life in children with hereditary multiple endocrine neoplasia type 2A (codon 634) and 2BActa Endocrinologica, 2009
- Premonitory symptoms preceding metastatic medullary thyroid cancer in MEN 2B: An exploratory analysisSurgery, 2008
- Medullary thyroid carcinoma in a 2-month-old male with multiple endocrine neoplasia 2B and symptoms of pseudo-Hirschsprung disease: a case reportJournal of Pediatric Surgery, 2007
- Two Germline Missense Mutations at Codons 804 and 806 of the RET Proto‐oncogene in the Same Allele in a Patient with Multiple Endocrine Neoplasia Type 2B without Codon 918 MutationJapanese Journal of Cancer Research, 1999
- Germline Dinucleotide Mutation in Codon 883 of theRETProto-Oncogene in Multiple Endocrine Neoplasia Type 2B Without Codon 918 MutationJournal of Clinical Endocrinology & Metabolism, 1997
- Germline mutation of RET codon 883 in two cases of de novo MEN 2BOncogene, 1997
- The Relationship Between Specific RET Proto-oncogene Mutations and Disease Phenotype in Multiple Endocrine Neoplasia Type 2JAMA, 1996