Primary High Grade Non-Anaplastic Thyroid Carcinoma: A Retrospective Study of 364 Cases.

Abstract

BACKGROUND\nHigh grade non-anaplastic thyroid carcinomas (HGTC) are carcinomas of follicular cells with prognosis intermediate between well-differentiated and anaplastic carcinoma.\n\n\nMETHODS\nThis study includes 364 HGTC patients: 200 patients (54.9%) were diagnosed as poorly differentiated thyroid carcinoma based on Turin consensus (HGTC-PDTC) and 164 with high grade features that did not meet Turin criteria (HGTC-nonPDTC).\n\n\nRESULTS\nHGTC are aggressive: 3-year, 5-year, 10-year, and 20-year disease specific survival (DSS) were 89%, 76%, 60% and 35% respectively. Although DSS was similar between HGTC-PDTC and HGTC-nonPDTC, HGTC-PDTC was associated with higher rate of RAI avidity, higher frequency of RAS mutations, lower rate of BRAF V600E mutations, and higher propensity for distant metastasis (DM) compared with HGTC-nonPDTC. Independent clinicopathologic markers of worse outcome were older age, male sex, extensive necrosis, lack of encapsulation for DSS; older age, male sex, vascular invasion for DM free survival; older age, necrosis, positive margin, lymph node metastasis for locoregional recurrence free survival. The frequency of BRAF, RAS, TERT, TP53, and PTEN alterations was 28%, 40%, 55%, 11%, and 10%, respectively. TP53, PTEN, and TERT were independent molecular markers associated with unfavorable outcome independent of clinicopathologic parameters. Coexistence of BRAF V600E and TERT promoter mutation increased the risk of DM.\n\n\nCONCLUSIONS\nThe above data supports the classification of high grade non-anaplastic thyroid carcinoma as a single group with two distinct subtypes based on tumor differentiation: HGTC-PDTC and HGTC-nonPDTC.