Villous papillary thyroid carcinoma: a variant associated with marfan syndrome

Endocr Pathol. 2012 Dec;23(4):254-9. doi: 10.1007/s12022-012-9219-6.

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.

Publication types

  • Case Reports

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Carcinoma / pathology*
  • Carcinoma, Papillary
  • Cyclin D1
  • Epithelial-Mesenchymal Transition / genetics
  • Galectin 3 / metabolism
  • Humans
  • Keratin-19 / metabolism
  • Male
  • Marfan Syndrome / genetics
  • Marfan Syndrome / metabolism
  • Marfan Syndrome / pathology*
  • Middle Aged
  • Mutation*
  • Phosphorylation
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proto-Oncogene Proteins B-raf / genetics*
  • Signal Transduction
  • Smad Proteins / metabolism
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology*
  • Transforming Growth Factor beta / metabolism*

Substances

  • Biomarkers, Tumor
  • CCND1 protein, human
  • Galectin 3
  • HBME-1 antigen
  • Keratin-19
  • Proliferating Cell Nuclear Antigen
  • Smad Proteins
  • Transforming Growth Factor beta
  • p27 antigen
  • Cyclin D1
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf