High-Grade Non-Anaplastic Thyroid Carcinomas of Follicular Cell Origin: A Review of Poorly Differentiated and High-Grade Differentiated Carcinomas.

Poorly differentiated thyroid carcinoma (PDTC) and high-grade differentiated thyroid carcinoma (HGDTC) are considered high-grade follicular-derived thyroid carcinomas, with prognoses intermediate between well-differentiated and anaplastic thyroid carcinoma. Both share the presence of invasion, thyroid follicular-cell origin, and tumor necrosis or increased mitoses (≥ 3 mitoses per 2 mm² in PDTC and ≥ 5 mitoses per 2 mm² in HGDTC), without anaplastic dedifferentiation. PDTC must possess solid, trabecular, or insular growth and lack classic papillary-like nuclei; HGDTC can be of any architectural or nuclear morphology (follicular-like, papillary-like, oncocytic). Transformation may be accompanied by acquisition of high-risk mutations (such as TP53 or TERT promoter) on top of RAS-like or BRAF p.V600E-like (including NTRK-fusion) initial driver mutations. These carcinomas most frequently affect adults and often present with metastases (20-50%) or wide local invasion. As PDTC and HGDTC may be radioactive iodine resistant, post-surgical therapy may consist of external beam radiotherapy or targeted, mutation-dependent chemotherapy, such as tyrosine kinase inhibitors. Ten-year disease specific survival is as low as 50%. Awareness of high-grade features in the diagnostic setting is important for patient prognosis and triage of tissue for molecular analysis in order to guide relevant clinical management and therapy.