Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAF^V600E mutation

Background: Diffuse lymphocytic infiltration (DLI) is frequently found with papillary thyroid cancer (PTC), so there has been long interest in how it affects the characteristics of PTC. This purpose of this study was to define the association between DLI and PTC aggressiveness according to thyroperoxidase antibody (TPOAb) and B-type Raf (BRAF)^V600E mutation positivity.

Methods: There were 1879 patients with PTC who underwent surgery and were enrolled in this study. Clinicopathologic characteristics were compared between groups according to the presence of DLI and TPOAb. Multiple logistic regression analysis was conducted to assess odds ratio (OR) for each dependent variable (BRAF^V600E mutation, tumor size >1.0 cm, multifocality, extrathyroidal extension, and lymph node metastasis) of each group according to the presence of DLI and TPOAb, with the group with neither DLI or TPOAb (DLI-negative TPOAb-negative PTC) as the reference.

Results: The DLI-positive PTC showed more frequent multifocality and less frequent BRAF^V600E mutation than DLI-negative PTC. Among patients with DLI-positive PTC, extrathyroidal extension and BRAF^V600E mutation was less frequent when serum TPOAb was positive. In multiple logistic regressions, DLI-positive TPOAb-positive PTC showed a high OR for multifocality (1.410; P = .017), but low ORs for BRAF^V600E mutation (0.521; P < .001) and extrathyroidal extension (0.691; P = .008). The patients with DLI-positive TPOAb-positive PTCs showed a high OR for multifocality (1.588; P = .002), and high ORs for tumor size >1.0 cm (2.205; P = .019) and lymph node metastasis (2.005; P = .032) in subgroup analyses of PTC with wild-type BRAF. The DLI-negative TPOAb-positive group was not associated with any tumor aggressiveness-related variables.

Conclusion: Although DLI was associated with multifocality regardless of TPOAb positivity, it was associated with an indolent feature when TPOAb was positive but with aggressive features in PTC with wild-type BRAF when TPOAb was negative. The TPOAb and BRAF status may help to define the clinical implication of lymphocytic infiltration found with PTC.