Interplay and clinicopathological correlates of tumor size, multifocality and aggressive variants in patients with operated differentiated thyroid carcinoma: A retrospective cohort study

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Abstract
Objectives: To investigate the interplay and clinicopathological correlates of tumor size, cancer foci (multifocality/bilaterality), and aggressive variants in patients with operated differentiated thyroid cancer (DTC). Methods: A total of 596 patients with operated DTC (median age: 47.0 (range: 18.0-87.0 years, 77.5% were females) were included in this retrospective cohort study. Data on patient demographics, cancer foci, concomitant Hashimoto's thyroiditis, surgery type, DTC subtype (papillary thyroid cancer [PTC], follicular thyroid cancer [FTC]) and variants, tumor size, lymph node metastasis, tumor invasion were recorded. Results: PTC aggressive variant (21.9%, P=0.045), extrathyroidal invasion (24.6%, P=0.012), tall cell PTC variant (60.3%, P=0.043), and widely invasive FTC variants (60.0% P=0.002) rates were significantly higher in the bilateral multifocal tumors than in the unifocal and unilateral multifocal tumors. The rates of Hashimoto's thyroiditis (59.8%, P<0.001) and PTC subtype (99.6%, P<0.001) were significantly higher, while the rates of lymph node metastasis (5.8%, P<0.001), capsule invasion (11.6%, P<0.001), vascular invasion (0.4%, P<0.001) and extrathyroidal invasion (4.5%, P<0.001) were significantly lower in 10 mm tumors. Presence vs. absence of PTC aggressive variant was associated with significantly higher greatest tumor size (12 mm, P=0.013) and higher rates of multifocal tumor (50.5%, P=0.013) and extrathyroidal invasion (33.0%, P<0.001). Conclusions: Our findings revealed the presence of bilaterality/multifocality and aggressive variants in a considerable proportion of patients with operated DTC, and a multifaceted interplay between bilaterality/multifocality, tumor size, and PTC aggressive variants, in addition to their individual effects on increased risk of tumor invasion, particularly the extrathyroidal invasion.

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