Columnar Cell Subtype of Papillary Thyroid Carcinoma Is Characterized By A High Frequency of High-Grade Tumors That Exhibit Aggressive Clinicopathologic Features and Poor Outcomes: A Multicenter Study of 71 Cases.

Papillary thyroid carcinoma, columnar cell subtype (PTC-CC) is a PTC characterized by nuclear pseudostratification and elongation. High-grade differentiated thyroid carcinoma is a novel classification of the WHO classification, defined by mitotic count ≥5/2 mm 2 and/or tumor necrosis, which may exhibit CC morphology and can be termed as high-grade PTC-CC (HGPTC-CC). In this multicenter retrospective study, we conducted a detailed clinicopathologic review in a retrospective cohort of 71 PTC-CC and HGPTC-CC. HGPTC-CC was common among tumors showing columnar cell morphology, accounting for 46% (33/71) of the entire cohort. Compared with PTC-CC, HGPTC-CC was significantly associated with male sex, infiltrative tumors, angioinvasion, microscopic extrathyroidal extension (ETE), positive resection margin, and advanced pT stage. Furthermore, HGPTC-CC had significantly shortened disease-specific survival (DSS), distant metastasis-free survival (DMFS), and regional recurrence-free survival (RRFS). The 10-year DSS was 95% and 57%, the 10-year DMFS was 87% and 26%, and the 10-year RRFS was 85% and 55% for PTC-CC and HGPTC-CC, respectively. Among tumors with known BRAFV600E and RASQ61R status, BRAFV600E mutation was detected in 40% (19/47), whereas RASQ61R was identified in 15% (6/39). HGPTC-CC was associated with a significantly higher percentage of RASQ61R (PTC-CC 4%, HGPTC-CC 36%). In conclusion, a significant percentage (46%) of PTC-CCs are high-grade. HGPTC-CC is associated with adverse clinicopathologic features and poor outcomes. The impression of PTC-CC as an aggressive PTC subtype may be attributed to the high prevalence of high-grade histology in these tumors. Careful examination for mitoses and necrosis is required for accurate diagnosis and prognostication in PTC-CC.