title: Villous papillary thyroid carcinoma: a variant associated with marfan syndrome.
abstract: Marfan syndrome (MFS) is an autosomal dominant hereditary disorder of connective tissue associated with perturbations in transforming growth factor β (TGF-β) biology, most often due to mutations in FBN1 gene that encodes fibrillin-1. To our knowledge, there is no known association of MFS with thyroid carcinoma. We report a 46-year-old man with known history of MFS who developed an unusual histological variant of papillary thyroid carcinoma. The tumor exhibited a widely invasive florid papillary growth pattern with prominent long villous fronds. Immunohistochemical and molecular analysis revealed a BRAF(V600E) mutation, evidence of aggressive biomarker expression (positivity for HBME-1, cytokeratin 19, galectin-3 and cyclin D1, and loss of p27), and changes associated with TGF-β-related epithelial-to-mesenchymal transition with active phospho-SMAD signaling. We introduce a unique histological pattern of papillary thyroid carcinoma that is associated with MFS. The combination of BRAF(V600E) mutation in the setting of altered TGF-β signaling and weak connective tissue integrity associated with MFS may cooperate and possibly be responsible to form this unique villous morphology with epithelial-to-mesenchymal transition and invasive growth.
authors: Department of Pathology, University Health Network, Toronto, ON, Canada.
authors: Daniel A
authors: DA
authors: Winer
authors: Shawn
authors: S
authors: Winer
authors: Lorne
authors: L
authors: Rotstein
authors: Sylvia L
authors: SL
authors: Asa
authors: Ozgur
authors: O
authors: Mete
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002291:Carcinoma, Papillary; D019938:Cyclin D1; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D037502:Galectin 3 / Q000378:metabolism; D006801:Humans; D053539:Keratin-19 / Q000378:metabolism; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D000951:Antigens, Neoplasm
chemical_list: D014408:Biomarkers, Tumor; D019938:Cyclin D1; D037502:Galectin 3; D053539:Keratin-19; D018809:Proliferating Cell Nuclear Antigen; D048493:Proto-Oncogene Proteins B-raf; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C530104:CCND1 protein, human; C432845:HBME-1 antigen; D000951:Antigens, Neoplasm; C413374:p27 antigen; C482119:BRAF protein, human