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Villous Papillary Thyroid Carcinoma: a Variant Associated with Marfan Syndrome

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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 BRAFV600E 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 BRAFV600E 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.

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Authors and Affiliations

  1. Department of Pathology, University Health Network, 200 Elizabeth Street, 11th floor, Toronto, ON, Canada, M5G 2C4

    Daniel A. Winer, Shawn Winer, Sylvia L. Asa & Ozgur Mete

  2. Department of General Surgery, University Health Network, Toronto, ON, Canada, M5G 2C4

    Lorne Rotstein

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  1. Daniel A. Winer
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  2. Shawn Winer
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  4. Sylvia L. Asa
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  5. Ozgur Mete
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Correspondence to Ozgur Mete.

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Winer, D.A., Winer, S., Rotstein, L. et al. Villous Papillary Thyroid Carcinoma: a Variant Associated with Marfan Syndrome. Endocr Pathol 23, 254–259 (2012). https://doi.org/10.1007/s12022-012-9219-6

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