Influence of Lymphocytic Thyroiditis at Histology and Serum Thyroglobulin Autoantibodies on the Course of Papillary Thyroid Carcinoma

PURPOSE Papillary thyroid carcinoma (PTC) is frequently associated with diffuse lymphocytic thyoiditis (LT) at histology and serum autoantibodies to thyroglobulin (TgAb) and to thyroperoxidase (TPOAb). The influence of LT and thyroid autoantibodies on the prognosis of PTC is debated. We evaluated the clinical course of a large group of PTC patients according to the presence or absence of LT (LT+ and LT-) and thyroid autoantibodies. METHODS We evaluated 194 consecutive and non-selected PTC patients treated with total thyroidectomy plus ¹³¹I ablation between 2007 and 2009, followed for 7.2 years (mean). 72 patients had follicular variant of PTC, 97 classic, 16 tall cells and the remaining 9 others variants (solid or oxyphilic cells). LT was diagnosed in presence of >10 lymphocytes/field (40x). At the time of ablation, all patients underwent measurement of Tg, TgAb and TPOAb, neck ultrasound and whole body scan. After ablation, patients underwent Tg (Beckman Coulter), TgAb and TPOAb (Tosoh) measurement and neck ultrasound (associated with other imaging if required) every 6-12 months. PTC was considered in remission according to the following criteria: un-stimulated Tg <0.2 ng/mL or stimulated Tg <1 ng/mL with TgAb <8 IU/mL and no evidence of structural disease. PTC was considered as persistent when un-stimulated Tg was ≥0.2 ng/mL or stimulated Tg was ≥1 ng/mL, or when TgAb were ≥8 IU/mL, or there was evidence of structural disease. RESULTS LT was found in 47% of patients, with a F/M ratio of 6.6/1, and was associated with a hypoechoic pattern at thyroid ultrasound (p = 0.05). At the end of follow-up 44/194 (22.7%) had persistent disease. Among them, 17/72 (23.6%) were follicular, 19/97 (19.6%) classic, 6/16 (37.5%) tall cells and 2/9 (22.2%) other variants. The time to remission was longer in the LT+ compared to the LT- patients (19.5 vs 7.5 months) (median) (p <0.001), in TgAb positive compared to TgAb negative patients (28.5 vs 7.5 months) (p <0.001) and in TPOAb positive compared to TPOAb negative patients (28.0 vs 8.0 months) (p = 0.005). At multivariate analysis TgAb were the only independent factor influencing the time to remission (0.54; 0.35-0.83; HR and confidence interval) (p = 0.001). However, evaluating only the 111 TgAb negative patients, the time to remission (undetectable un-stimulated or stimulated Tg and no evidence of structural disease) was similar in the LT+ and LT- groups (8.0 months for both). At variance, in 83 TgAb positive patients the time to remission was longer in LT+ than in LT- patients (29.3 vs 13.0 months) (p=0.01). CONCLUSIONS The time to remission is longer in LT+ compared to LT- PTC patients treated with total thyroidectomy plus ¹³¹I ablation. This is due to the frequent association of LT with TgAb, because undetectable TgAb is required to define the remission of PTC. Indeed, coexistent LT does not influence the time to remission when the analysis is restricted to TgAb negative patients.