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.
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 mm2 and/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.
Haukur Einarsson, M.D.
Resident, Anatomic and Clinical Pathology
Michael Rivera, M.D.
Consultant, Anatomic Pathology
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science