title: Surgical curability of medullary thyroid cancer in multiple endocrine neoplasia 2B: a changing perspective.
abstract: OBJECTIVE
  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).
  
  
  BACKGROUND
  MEN 2B patients, running a high risk of metastatic MTC, must be diagnosed early for biochemical cure.
  
  
  METHODS
  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.
  
  
  RESULTS
  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%).
  
  
  CONCLUSIONS
  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.
authors: *Department of General, Visceral and Vascular Surgery, University of Halle, Halle, Germany †Department of Surgery, Haukeland University Hospital, University of Bergen, Bergen, Norway ‡Department of Surgical Sciences, University of Bergen, Bergen, Norway §Medical Faculty, University of Oslo, Oslo, Norway ¶Central Laboratory, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors: Michael
authors: M
authors: Brauckhoff
authors: Andreas
authors: A
authors: Machens
authors: Kerstin
authors: K
authors: Lorenz
authors: Trine
authors: T
authors: Bjøro
authors: Jan Erik
authors: JE
authors: Varhaug
authors: Henning
authors: H
authors: Dralle
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000601:surgery; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D018278:Carcinoma, Neuroendocrine; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D018814:Multiple Endocrine Neoplasia Type 2b / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery; D009154:Mutation; D037981:Neck Dissection; D010673:Pheochromocytoma / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000601:surgery; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000601:surgery*; D013965:Thyroidectomy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human