Primary Benign and Malignant Thyroid Neoplasms With Signet Ring Cells: Cytologic, Histologic, and Molecular Features

Am J Clin Pathol. 2017 Sep 1;148(3):251-258. doi: 10.1093/ajcp/aqx074.


Objectives: Signet ring cells (SRCs) can be seen in a variety of thyroid tumors and can pose a diagnostic pitfall on cytology. This study describes the cytologic, histomorphologic, and molecular aspects of a cohort of primary thyroid tumors with SRCs.

Methods: A search was performed of the Massachusetts General Hospital and Brigham and Women's Hospital (Boston, MA) pathology archives for the keywords thyroid, signet, and signet ring features between 2000 and 2014. Seven thyroidectomy specimens with corresponding thyroid fine-needle aspiration (FNA) were obtained. Cytology and histopathology slides were evaluated. Molecular analysis was performed using anchored multiplex polymerase chain reaction (AMP).

Results: The cohort consisted of four follicular adenomas (FAs), two noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), and one secretory carcinoma (SC). The FNA diagnoses were atypia of undetermined significance (n = 3), suspicious for follicular neoplasm (n = 3), and suspicious for malignancy (n = 1). Molecular analyses revealed PTEN and FGFR3 mutations in an FA and NIFTP, respectively, and an ETV6-NTRK3 fusion in a case of primary thyroid gland SC.

Conclusions: Our study demonstrates the range of thyroid tumors with SRCs. While most thyroid tumors with SRCs are benign, primary thyroid SC should also be considered in the differential diagnosis.

Keywords: Cytopathology; Fine-needle aspiration; Molecular testing; Secretory carcinoma of thyroid; Signet ring cells; Thyroid.

MeSH terms

  • Adenocarcinoma, Follicular / metabolism
  • Adenocarcinoma, Follicular / pathology*
  • Adenocarcinoma, Follicular / surgery
  • Adenoma / metabolism
  • Adenoma / pathology*
  • Adenoma / surgery
  • Adolescent
  • Aged
  • Aged, 80 and over
  • Biopsy, Fine-Needle
  • Diagnosis, Differential
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • PTEN Phosphohydrolase / metabolism
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology*
  • Thyroid Neoplasms / surgery
  • Thyroidectomy


  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3
  • PTEN Phosphohydrolase
  • PTEN protein, human