Signet ring cell variant of follicular thyroid carcinoma: Report of two cases with focus on morphological, expressional and genetic characteristics

Diagn Pathol. 2019 Nov 7;14(1):127. doi: 10.1186/s13000-019-0904-3.


Background: Follicular thyroid carcinoma (FTC) is a neoplasm that presents with a micro-follicular growth pattern and a neutrally stained cytoplasm. Seldom, FTCs display unusual morphological characteristics - but given the rarity of these histological subtypes, little is known regarding the underlying genetics and the coupling to patient outcome.

Case presentation: We present two extremely rare cases of minimally invasive FTC with signet ring cell morphology (SRC-FTC) and describe the cytological, microscopic, immunohistochemical and molecular features for both tumors. Both were male patients, age 71 and 51 respectively. The preoperative cytology for both cases could not pinpoint a clear-cut signet ring cell morphology, but a tendency towards nuclear marginalization was seen. The tumors were 38 mm and 22 mm respectively and displayed evident signet ring cell features in subsets of tumor cells as well as degenerative stromal changes. The tumor cells were positive for TTF1, PAX8 and thyroglobulin, and the proliferation indexes were 4% and 1,9% respectively. Both tumors displayed capsular invasion, but not lymphovascular invasion. The tumors were sequenced for mutations in the TERT promoter and 22 additional cancer-related genes, interestingly; one patient was shown to carry a deleterious intronic variant in PTEN, a tumor suppressor gene coupled to thyroid tumorigenesis and Cowden syndrome. Both patients are alive and well awaiting postoperative radioiodine treatment.

Conclusions: The SRC-FTCs described herein were small, TERT promoter wildtype tumors exhibiting low proliferation, thereby suggesting that these exceedingly rare lesions probably carry a favorable prognosis - although the scarce availability regarding descriptions of this tumor entity nevertheless might justify careful clinical monitoring and mandate investigations in larger case series.

Keywords: Follicular thyroid cancer; PTEN; Signet ring cell.

MeSH terms

  • Adenocarcinoma, Follicular / pathology
  • Adenocarcinoma, Follicular / radiotherapy*
  • Aged
  • Carcinoma, Signet Ring Cell / diagnosis
  • Carcinoma, Signet Ring Cell / pathology*
  • Cell Nucleus / drug effects
  • Cell Nucleus / pathology
  • Diagnosis, Differential
  • Humans
  • Iodine Radioisotopes / therapeutic use
  • Male
  • Mutation / genetics
  • Thyroid Gland / drug effects*
  • Thyroid Gland / pathology
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / radiotherapy*


  • Iodine Radioisotopes