Macrofollicular variant follicular thyroid tumors are DICER1 mutated and exhibit distinct histological features

Histopathology. 2021 Oct;79(4):661-666. doi: 10.1111/his.14416. Epub 2021 Aug 3.


Aims: DICER1 germline mutations cause DICER1 syndrome, in which multinodular goitre is a common feature. Recently, somatic DICER1 mutations have been reported in sporadic thyroid carcinomas, of which the newly described macrofollicular variant of follicular thyroid carcinoma (MV-FTC) seems particularly enriched for this aberrancy. We report here histological and genetic findings in five follicular thyroid tumours with macrofollicular architecture (four carcinomas and one adenoma).

Methods and results: We have diagnosed five cases during a year-long period at the Karolinska University Hospital, a tertiary thyroid cancer center with a catchment area of approximately 2.3 million inhabitants. Tumour DNA was interrogated using a commercially available massive parallel sequencing platform. All cases were female patients, ranging from 13 to 33 years at surgery. A single patient was a DICER1 syndrome carrier; the others were sporadic cases. All tumours displayed a macrofollicular architecture with a broad capsule. The MV-FTCs displayed capsular invasion, but never vascular invasion. Areas with degenerative changes (microinfarctions) were noted in all cases, and focal papillary growth was observed in the majority. The Ki-67 proliferation index was always above 4%. All cases displayed DICER1 gene mutations, of which four of five cases displayed RNase IIIb hot-spot missense mutations adjoined by a second, deleterious variant in three of five tumouurs.

Conclusions: Macrofollicular variants of follicular thyroid tumours are predominantly found in younger females and are strongly linked to somatic DICER1 gene mutations. Histological features such as a broad tumorous capsule, focal infarctions and areas with papillae could constitute clues prompting further genetic analyses.

Keywords: DICER1; follicular thyroid carcinoma; histology; macrofollicular variant; mutation.

MeSH terms

  • Adenocarcinoma, Follicular / genetics*
  • Adenocarcinoma, Follicular / pathology
  • Adenoma / genetics*
  • Adenoma / pathology
  • Adolescent
  • Adult
  • DEAD-box RNA Helicases / genetics*
  • Female
  • Germ-Line Mutation
  • Humans
  • Ribonuclease III / genetics*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology


  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases

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