Clinicopathologic and Molecular Features of Poorly Differentiated Thyroid Carcinomas in Adults ≤ 45 Years of Age

The clinical behavior and molecular underpinnings of rare cases of poorly differentiated thyroid carcinoma (PDTC) diagnosed in young adults are not established. We evaluated 13 cases of PDTC in adult patients ≤ 45 years of age. The median age at diagnosis was 40 years (range 27 - 45 years). The median tumor size was 3.7 cm. The median mitotic count was 6 per 2 mm². Necrosis was present in 7 (54%) cases. Eleven (85%) cases were either encapsulated with extensive (≥ 4 foci) angioinvasion or widely invasive. Molecular analysis was available for nine (69%) cases and revealed two (22%) with PAX8::PPARG fusions, two (22%) with NRAS alterations, one (11%) with a DICER1 variant, one (11%) with alterations in ATM, CDKN1A and TERT, one (11%) with a TSC2 deletion and TERT copy number gain, and two (22%) with variants of uncertain significance only. Of the 12 (92%) patients with follow-up data available (median 6.2 years, range 1.5-16.4 years), the only patient who died of disease had distant metastases at diagnosis. Of the remaining patients with initial M0 disease, only one had disease recurrence, developing local recurrence and distant metastasis with persistent disease at last follow up. Our findings suggest that PDTC in adults ≤ 45 years of age at diagnosis, may have a better prognosis than is typically associated with PDTC despite high-grade features and invasive growth. Additionally, we found a higher rate of PAX8::PPARG fusions and a lower rate of TERT alterations, suggesting that the molecular profile might explain the improved survival.