Ectopic Thyroid Tissue: Immunohistochemistry and Molecular Analysis

Appl Immunohistochem Mol Morphol. 2018 Nov/Dec;26(10):734-739. doi: 10.1097/PAI.0000000000000515.


Ectopic thyroid tissue is rare and controversial. Some experts consider it to always be metastatic thyroid carcinoma, whereas others consider it benign as long as it is restricted to few follicles without cytoarchitectural features of papillary thyroid carcinoma. Immunohistochemistry (IHC) and molecular studies have not yet been performed to further characterize this entity. We retrospectively searched our pathology files for all ectopic thyroid inclusions and reviewed clinicopathologic characteristics and concurrent thyroid pathologic findings. We identified 8 cases from 7 patients. Ectopic thyroid tissue was present in the following locations: neck soft tissue: 3, thymus: 2, neck lymph nodes: 2, perihilar soft tissue: 1. All patients had histologically benign thyroid specimens. BRAFV600E (VE1) IHC, HBME-1 IHC, galectin-3 IHC, BRAFV600E allele-specific polymerase chain reaction (PCR) and NRAS/KRAS pyrosequencing were performed. To assess the sensitivity and specificity of BRAFV600E IHC compared with PCR; we tested 13 cases of primary and metastatic papillary and follicular thyroid carcinomas. All the ectopic cases were HBME-1, galectin-3, BRAFV600E (IHC, PCR), and NRAS/KRAS mutation negative (specificity=100%). Compared with PCR, BRAF IHC had 89% sensitivity and 100% specificity. Lack of common carcinoma-associated mutations supports benign nature of this entity. BRAF, HBME-1, and galectin-3 IHC are accurate and helpful when not enough tissue is available for molecular studies. IHC and molecular studies are more helpful than morphology alone in identifying benign thyroid rests.

MeSH terms

  • Adenocarcinoma, Follicular* / genetics
  • Adenocarcinoma, Follicular* / metabolism
  • Adenocarcinoma, Follicular* / pathology
  • Adult
  • Aged
  • Amino Acid Substitution
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Blood Proteins
  • Female
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • Galectin 3 / genetics
  • Galectin 3 / metabolism
  • Galectins
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Middle Aged
  • Mutation, Missense
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Retrospective Studies
  • Sensitivity and Specificity
  • Thyroid Gland* / metabolism
  • Thyroid Gland* / pathology
  • Thyroid Neoplasms* / genetics
  • Thyroid Neoplasms* / metabolism
  • Thyroid Neoplasms* / pathology


  • Biomarkers, Tumor
  • Blood Proteins
  • Galectin 3
  • Galectins
  • HBME-1 antigen
  • KRAS protein, human
  • LGALS3 protein, human
  • Membrane Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • GTP Phosphohydrolases
  • NRAS protein, human
  • Proto-Oncogene Proteins p21(ras)