The prognostic impact of blood vessel invasion in infiltrative papillary thyroid carcinoma: a retrospective case–control study

Aims Papillary thyroid carcinoma (PTC) with blood vessel invasion (BVI) is classified as intermediate risk by the American Thyroid Association (ATA). However, no publications have adequately distinguished between encapsulated follicular variant (EFV) of PTC and infiltrative PTC with regard to BVI. Recently, the WHO classification reclassified EFV of PTC, a RAS‐like tumour, as a distinct entity from PTC. In this study, we aimed to investigate the prognostic impact of BVI in infiltrative PTC. Methods and results This retrospective matched case–control study included 134 cases of infiltrative PTC with BVI and at least 1 year of follow‐up. A 1:1 matched control group of 134 infiltrative PTC without BVI, matched for PTC subtype and AJCC stage, was also included. CD31 and D2‐40 immunohistochemistry were performed on 195 blocks to distinguish BVI from lymphatic vessel invasion (LI). BVI was defined as a CD31‐positive/D2‐40‐negative endothelium‐lined tumour embolus within a vessel wall, whereas LI was defined as a free‐floating tumour plug lacking an endothelial lining within a CD31/D2‐40‐positive vessel. The median follow‐up period was 5.3 years. Extensive BVI was the only independent adverse prognostic factor for disease‐free survival (hazard ratio = 3.531) on multivariate survival analysis. On univariate analysis, infiltrative PTC with extensive BVI was associated with significantly decreased distant metastasis‐free survival compared with those without BVI or with focal BVI. Conclusions Using CD31 and D2‐40 as gold standard ancillary tools, we established reliable histologic criteria to differentiate BVI from LI. Extensive BVI is an independent adverse prognostic factor in infiltrative BRAF V600E‐like PTC and should therefore be considered in initial risk stratification for infiltrative PTC.