C Cell and Follicular Epithelial Cell Precursor Lesions of the Thyroid

Arch Pathol Lab Med. 2017 Dec;141(12):1646-1652. doi: 10.5858/arpa.2016-0399-RA. Epub 2017 Jun 23.


Context: - The identification of precursor or dysplastic lesions in the thyroid is difficult. Pathology of the C cell has been extensively studied, and the preneoplastic nature of C-cell hyperplasia in the setting of familial medullary thyroid carcinomas is well established. However, the distinction between neoplastic and physiologic/reactive C-cell hyperplasia remains a challenge. Unlike C cells, the existence of a precursor lesion of follicular cell-derived tumors is less well established, and a dysplastic or preneoplastic follicular lesion has not been well defined.

Objective: - To discuss putative precursor lesions in the thyroid arising from C cells and follicular epithelial cells.

Data sources: - Data were obtained from a review of the pertinent peer-reviewed literature.

Conclusions: - Although the preneoplastic nature of C-cell hyperplasia in the setting of familial medullary thyroid carcinoma is well recognized, the preneoplastic nature/malignant potential of reactive/physiologic C-cell hyperplasia and its role in the development of sporadic, medullary thyroid carcinoma is still unclear. Current data suggest that benign follicular lesions may have malignant potential, and there may be a multifocal progression from benign to malignant. Atypical follicular lesions in the background of chronic lymphocytic thyroiditis may represent dysplastic or premalignant lesions.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Medullary / congenital
  • Carcinoma, Medullary / pathology
  • Carcinoma, Neuroendocrine / pathology
  • Diagnosis, Differential
  • Epithelial Cells / pathology
  • Humans
  • Hyperplasia / pathology
  • Multiple Endocrine Neoplasia Type 2a / pathology
  • Mutation
  • Precancerous Conditions / genetics
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology*
  • Thyroid Diseases / pathology*
  • Thyroid Gland / pathology*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology*


  • Biomarkers, Tumor

Supplementary concepts

  • Familial medullary thyroid carcinoma
  • Thyroid cancer, medullary