Molecular basis off hurthle cell papillary thyroid carcinoma

J Clin Endocrinol Metab. 2000 Feb;85(2):878-82. doi: 10.1210/jcem.85.2.6404.


Among thyroid neoplasms, Hurthle cell tumors (HCTs) have traditionally been a distinct diagnostic category. Hurthle cell adenomas are encapsulated follicular lesions with benign behavior. Hurthle cell carcinomas exhibit unequivocal capsular and/or vascular invasion; they are aggressive tumors with a poor prognosis. Recently, Hurthle cell papillary thyroid carcinomas (PTCs) have been identified on morphological grounds. We hypothesize that a subset of HCTs represent PTC with clinical, histological, and immunohistochemical features based on specific molecular events. ret/PTC gene rearrangements give rise to novel oncogenes that are unique to PTC. We studied a group (n = 50) of HCTs for ret/PTC gene rearrangements. Tumors were examined for papillary differentiation by light microscopic evaluation of nuclear features, by RT-PCR for ret/PTC gene rearrangements, and by immunohistochemistry for ret. Among 24 noninvasive tumors, 13 contained ribonucleic acid for ret/PTC-1, -2, or -3, and 9 of these were immunoreactive for ret. Among 19 Hurthle cell carcinomas, 15 had focal nuclear hypochromasia with grooves and/or inclusions; expressed transcripts of ret/PTC-1, -2, or-3; and exhibited ret positivity. Tumors with ret/PTC gene rearrangements tended to have lymph node metastases rather than hematogenous spread. Our results indicate that a subset of HCTs exhibit features of PTC that are attributable to specific gene rearrangements, resulting in expression of ret/PTC oncogenes. These data support subclassification of HCTs into three groups: Hurthle cell adenomas, Hurthle cell carcinomas, and Hurthle cell PTC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Papillary / diagnosis*
  • Adenocarcinoma, Papillary / genetics
  • Adenocarcinoma, Papillary / pathology
  • Adult
  • Aged
  • Female
  • Gene Rearrangement
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics
  • Thyroid Neoplasms / diagnosis*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology


  • Oncogene Proteins, Fusion