title: Synchronous metastatic medullary and papillary thyroid carcinomas in a patient with germline RET mutation: case report, molecular analysis, and implications for pathogenesis.
abstract: The occurrence of medullary thyroid carcinoma (MTC) in patients with germline RET mutation is well established, but the occasional occurrence of papillary thyroid carcinoma (PTC) in this setting remains unexplained. We report a case of synchronous MTC and PTC in a patient with germline RET mutation, and investigate the molecular pathogenesis of these two tumors. A 48-year-old man presented with cervical lymphadenopathy and was found to have metastatic MTC involving cervical and mediastinal lymph nodes. He underwent thyroidectomy and debulking of metastatic disease. The resected thyroid showed bilateral MTC and a 1-cm PTC. His lymph node metastases were predominantly MTC along with a small focus of metastatic PTC. Molecular testing using peripheral blood revealed a germline RET point mutation (Val804Met). Both tumors were analyzed for the BRAF (Val600Glu) mutation and the RET/PTC1 translocation. The PTC was positive for the BRAF mutation but negative for RET/PTC1. The MTC was negative for both abnormalities. We conclude that the MTC was caused by the germline RET mutation, while the PTC was caused by a somatic BRAF mutation. The occurrence of PTC in patients with germline RET mutations appears to be purely coincidental.
authors.affiliation: Department of Pathology, State University of New York Upstate Medical University, 750 E. Adams St, Syracuse, NY 13210, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Griffith
authors.forename: Shengle
authors.initials: S
authors.lastname: Zhang
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mukhopadhyay
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000473:pathology; D018095:Germ-Line Mutation; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf