MON-502 Clinical-Pathological and Molecular Prognostic Markers in Aggressive and Poorly Differentiated Thyroid Cancers; A Tertiary-Center Experience

Background: Aggressive variants of papillary thyroid cancer (AV-PTC) and poorly differentiated thyroid cancers (PDTC) are 2 malignancies that lie in between the well-differentiated and the undifferentiated anaplastic cancers. While management of those well-differentiated cancers is established in the literature, that of AV-PTC and PDTC is less clear as they behave different to their more benign counterparts. The aim of this study is to describe the clinico-pathologic characteristics and genotypic background of AV-PTC and PDTC and to assess their prognostic value. Methods: The charts of all patients with thyroid cancer in our center for the last 10 years were retrospectively reviewed. Those with AV-PTC and PDTC were selected and included in the analysis. Clinical presentation, pathologic characteristics, molecular markers, specific treatments and clinical outcomes were compared among groups. Results: Out of 3244 thyroid cancer charts reviewed, 87 patients met the criteria for AV-PTC (n=45) and PDTC (n=42). Mean age at diagnosis was 48.1 years (SD 17.8), with female predominance (64.4% vs 35.6%). Median duration of follow up was 3 years (0.1-30). Out of the 75 patients with follow up for more than a year, 42.7% had either persistent disease or recurrence (52.6% in AV-PTC and 32.4% in PDTC) and 4.1% died. Presence of vascular invasion was associated with higher rates of persistent or recurrent disease (74.1% in positive vascular invasion vs 20.5% in negative vascular invasion, p < 0.001). Recurrence rate was 0% in patients with Ki67 < 10% and 40% in those >= 10%. There was no difference in terms of recurrence based on presence of BRAF mutation (33% in BRAF+ & 29% in BRAF-, p=1), or percentage of aggressive/poorly differentiated tumor involvement (48% in > 30% involvement vs 28% in < 30%, p = 0.132). Discussion and conclusion: The prevalence of AV-PTC and PDTC in this cohort was low at 1.3% each, and the rate of patients with persistent or recurrent disease at 1 year after primary therapy was also similar to that reported (42.7%). The mortality rates, however, in our study is surprisingly lower than that expected elsewhere (4.1%), most likely attributed to a shorter follow up period. Patients with absent vascular invasion were less likely to have persistent or recurrent disease. Those with lower Ki67 (<10%) also had lower relapse rate, although, the p value was > 0.05. It is worth mentioning that even though there were higher rates of recurrence among those with > 30% tumor involvement, it did not reach statistical significance, supporting recent studies stating that even tumor involvement of > 10% can have adverse outcomes. In conclusion, AV-PTC and PDTC are relatively rare but aggressive tumors. Possible prognostic markers that can be used to guide therapy and monitoring include: vascular invasion, extra-thyroidal extension, response to primary therapy and the proliferative index Ki67.