Michael Brauckhoff1, Andreas Machens, Kerstin Lorenz, Trine Bjøro, Jan Erik Varhaug, Henning Dralle. 1. *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.
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.
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 2Bpatients, running a high risk of metastatic MTC, must be diagnosed early for biochemical cure. METHODS: Forty-four MEN 2Bpatients carrying inherited (3 patients) and de novo (41 patients) M918TRET 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: Samuel A Wells; Sylvia L Asa; Henning Dralle; Rossella Elisei; Douglas B Evans; Robert F Gagel; Nancy Lee; Andreas Machens; Jeffrey F Moley; Furio Pacini; Friedhelm Raue; Karin Frank-Raue; Bruce Robinson; M Sara Rosenthal; Massimo Santoro; Martin Schlumberger; Manisha Shah; Steven G Waguespack Journal: Thyroid Date: 2015-06 Impact factor: 6.568
Authors: Jonathan D Wasserman; Gail E Tomlinson; Harriet Druker; Junne Kamihara; Wendy K Kohlmann; Christian P Kratz; Katherine L Nathanson; Kristian W Pajtler; Andreu Parareda; Surya P Rednam; Lisa J States; Anita Villani; Michael F Walsh; Kristin Zelley; Joshua D Schiffman Journal: Clin Cancer Res Date: 2017-07-01 Impact factor: 12.531
Authors: Else Marie Opsahl; Lars Andreas Akslen; Ellen Schlichting; Turid Aas; Katrin Brauckhoff; Anne Irene Hagen; Alf Frimann Rosenlund; Eva Sigstad; Krystyna K Grøholt; Lars H Jørgensen; Trine Bjøro Journal: Eur Thyroid J Date: 2019-04-29
Authors: Else Marie Opsahl; Lars Andreas Akslen; Ellen Schlichting; Turid Aas; Katrin Brauckhoff; Anne Irene Hagen; Alf Frimann Rosenlund; Eva Sigstad; Krystyna K Grøholt; Lovise Mæhle; Lars Fredrik Engebretsen; Lars H Jørgensen; Jan Erik Varhaug; Trine Bjøro Journal: Eur Thyroid J Date: 2018-11-08