Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAFV600E mutation

• DOI: 10.1002/hed.25327
• Publication Date: 2018-06-23T06:45:56Z
• Authors: Young Ki Lee; Kyeong Hye Park; Se Hee Park; Kwang Joon Kim; Dong Yeob Shin; Kee Hyun Nam; Woong Youn Chung; Eun Jig Lee
• Keywords: Male; Proto-Oncogene Proteins B-raf; 610; Iodide Peroxidase; 03 medical and health sciences; 0302 clinical medicine; Hashimoto's thyroiditis; 616; Republic of Korea; Humans; Lymphocytes; Thyroid Neoplasms; Autoantibodies; Retrospective Studies; Middle Aged; 3. Good health; Thyroid Cancer, Papillary; Lymphatic Metastasis; Mutation; diffuse lymphocytic infiltration; papillary thyroid carcinoma; Thyroidectomy; Female; B-type Raf (BRAF); thyroid peroxidase antibody

AbstractBackgroundDiffuse 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.MethodsThere 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 (BRAFV600E 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.ResultsThe DLI‐positive PTC showed more frequent multifocality and less frequent BRAFV600E mutation than DLI‐negative PTC. Among patients with DLI‐positive PTC, extrathyroidal extension and BRAFV600E 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 BRAFV600E 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.ConclusionAlthough 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.