February 2023 – Endocrine Pathology

A 62-year-old man presented with dysphonia and was found to have a 6 cm right-sided thyroid mass, extending between the trachea and the esophagus, with involvement of the right recurrent laryngeal nerve and esophageal musculature.

Histologic sections showed diffuse involvement of the entire right thyroid lobe by multiple tumor foci (Figures 1-4). Mitotic count was up to 10 mitosis per 2 mm2 and both lymphatic invasion and angioinvasion was present.

Figure 1
Figure 2
Figure 3
Figure 4

What is the most likely diagnosis?

  • Poorly differentiated thyroid carcinoma.
  • Widely invasive follicular thyroid carcinoma.
  • Infiltrative follicular variant papillary thyroid carcinoma.
  • Differentiated high-grade follicular thyroid carcinoma.

The correct answer is ...

Differentiated high-grade follicular thyroid carcinoma.

Differentiated high-grade thyroid carcinoma (DHGTC) belongs to the category of high-grade follicular cell-derived thyroid carcinomas, which was first introduced in the 2022 version of the World Health Organization Classification of Tumours. This category encompasses both DHGTC and poorly differentiated thyroid carcinoma (PDTC). Both of these tumors exhibit high-grade features but do not have anaplastic differentiation. By definition, DHGTC retains the architectural pattern of lower-grade follicular cell-derived carcinomas (papillary, follicular, or solid pattern), but the mitotic count is ≥5 mitosis per 2 mmand/or tumor necrosis is present. On the other hand, diagnosis of PDTC is based on the Turin consensus criteria, which in addition to increased mitotic count and/or tumor necrosis, includes the presence of a solid/trabecular/insular growth pattern as well as the absence of conventional nuclear features of papillary thyroid carcinoma (PTC).

DHGTCs are subclassified according to their histologic features into DHGTC, papillary type or, rarely, DHGTC, follicular type. In our case the overall architectural and cytologic features were those of DHGTC, follicular type, given the follicular growth pattern, absence of cytologic features of PTC, and increased mitotic activity present. The tumor was also widely invasive, which is commonly observed with DHGTC, follicular type.

DHGTCs are aggressive tumors with survival rates in between lower-grade follicular cell-derived carcinomas and anaplastic thyroid carcinoma. The 5-year overall survival of DHGTCs is 50%-70%. Additionally, these tumors have a high frequency of extrathyroidal extension as well as lymph node and distant metastases.

Molecular studies have indicated that DHGTCs develop from lower-grade follicular cell-derived carcinomas. This is supported by the fact that DHGTCs retain mutations that are frequently found in lower-grade carcinomas, such as RAS and BRAFV600E, but they usually acquire additional mutations associated with aggressive behavior, such as TERT promotor mutations. The tumor mutational burden of DHGTCs is also intermediate, between that of lower-grade carcinomas and anaplastic thyroid carcinoma.


  1. WHO Classification of Tumours Editorial Board. Endocrine and neuroendocrine tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2022 [cited 2022 December 7]. (WHO classification of tumours series, 5th ed.; vol. 10). Available from: https://tumourclassification.iarc.who.int/chapters/53.
  2. Wong KS, Dong F, Telatar M, Lorch JH, Alexander EK, Marqusee E, Cho NL, Nehs MA, Doherty GM, Afkhami M, Barletta JA. Papillary thyroid carcinoma with high-grade features versus poorly differentiated thyroid carcinoma: an analysis of clinicopathologic and molecular teatures and outcome. Thyroid. 2021 Jun;31(6):933-940. doi:10.1089/thy.2020.0668. Epub 2021 Jan 19. PMID: 33143568.
  3. Xu B, David J, Dogan S, Landa I, Katabi N, Saliba M, Khimraj A, Sherman EJ, Tuttle RM, Tallini G, Ganly I, Fagin JA, Ghossein RA. Primary high-grade non-anaplastic thyroid carcinoma: a retrospective study of 364 cases. Histopathology. 2022 Jan;80(2):322-337. doi:10.1111/his.14550. Epub 2021 Oct 7. PMID: 34449926; PMCID: PMC9425734.
  4. Hiltzik D, Carlson DL, Tuttle RM, Chuai S, Ishill N, Shaha A, Shah JP, Singh B, Ghossein RA. Poorly differentiated thyroid carcinomas defined on the basis of mitosis and necrosis: a clinicopathologic study of 58 patients. Cancer. 2006 Mar 15;106(6):1286-95. doi:10.1002/cncr.21739. PMID: 16470605.

Haukur Einarsson, M.D.

Resident, Anatomic and Clinical Pathology 
Mayo Clinic

Michael Rivera, M.D.

Consultant, Anatomic Pathology
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.