Familial thyroid carcinoma: a diagnostic algorithm

Adv Anat Pathol. 2008 Nov;15(6):332-49. doi: 10.1097/PAP.0b013e31818a64af.


Thyroid carcinomas derived from follicular cells are the most common endocrine malignancies, and papillary thyroid carcinoma (PTC) is the most common type. Although, the majority of papillary and follicular thyroid carcinomas (FTCs) are sporadic, familial forms have been described in recent years. Familial syndromes are classified into familial medullary thyroid carcinoma and familial nonmedullary thyroid carcinoma. Multifocal papillary carcinoma is the most frequent presentation of familial nonmedullary thyroid carcinoma, and based on clinico-pathologic findings it is divided into 2 groups. The first includes familial syndromes characterized by a predominance of nonthyroidal tumors, such as familial adenomatous polyposis, PTEN-hamartoma tumor syndrome, Carney complex type 1, and Werner syndrome. The second group includes familial syndromes characterized by a predominance of NMTC, such as pure familial (f) PTC with or without oxyphilia, fPTC with papillary renal cell carcinoma, and fPTC with multinodular goiter. Medullary thyroid carcinoma is derived from calcitonin-producing C cells. The familial form accounts for 20% to 25% of cases, and is usually a component of multiple endocrine neoplasia (MEN) IIA or IIB, or presents as pure familial medullary thyroid carcinoma syndrome. C-cell hyperplasia is the precursor lesion of these heritable syndromes. Some characteristic morphologic findings should alert the pathologist of a possible familial cancer syndrome, which may lead to further molecular genetic evaluation.

Publication types

  • Review

MeSH terms

  • Adenomatous Polyposis Coli / genetics
  • Adenomatous Polyposis Coli / pathology
  • Adult
  • Algorithms
  • Carcinoma, Medullary / diagnosis
  • Carcinoma, Medullary / genetics
  • Carcinoma, Medullary / pathology
  • Carcinoma, Papillary / diagnosis
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary, Follicular / diagnosis
  • Carcinoma, Papillary, Follicular / genetics
  • Female
  • Hamartoma Syndrome, Multiple / pathology
  • Humans
  • Middle Aged
  • Multiple Endocrine Neoplasia Type 2a / pathology
  • Neoplastic Syndromes, Hereditary / diagnosis
  • Neoplastic Syndromes, Hereditary / genetics
  • PTEN Phosphohydrolase / genetics
  • Thyroid Neoplasms / classification
  • Thyroid Neoplasms / diagnosis*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology


  • PTEN Phosphohydrolase