Hashimoto thyroiditis (HT) is a common finding in resected thyroid specimens.1 However, even though other aspects of HT have been extensively studied, there is still controversy on whether patients with papillary thyroid carcinoma (PTC) and concurrent HT are associated with favorable outcomes.2,3,4,5,6,7,8,9,10 Whereas several reports concluded that better prognosis was shown in the patients with the two diseases at the same time,4,6,7,11 the other reports conclude that HT was no significant prognostic factor predicting the outcome of PTC patients.2,3

Autoimmune thyroiditis, of which the pathologic hallmark is lymphocytic infiltration, can show a certain pathologic spectrum from lymphocytic infiltration only (chronic lymphocytic thyroiditis, CLT) to progressive loss of thyroid follicular cells, a concomitant replacement of the gland by lymphocytes, and the formation of germinal centers associated with fibrosis (HT).12 As the disease progresses the cellular infiltrate and the fibroblastic tissue increase, resulting in the disorganization and destruction of thyroid tissue.13 Therefore, this certain spectrum of pathologic features may affect the prognosis of PTC patients in different ways. To the best of our knowledge, no reports have compared CLT and HT with the prognosis of PTC. Therefore, our goal was to investigate the prognosis of PTC patients according to the presence of CLT or HT.

The Institutional Review Board of Severance Hospital approved this retrospective observational study and required neither patient approval nor informed consent for review of patients' images and medical records.

Clinicopathologic characteristics of the included 144 patients are summarized in Table 1. The follow-up period ranged from 38 to 92 months (mean, 68.9±8.1 months). Of the 144 patients, 41 had CLT and 19 had HT. There were 10 patients (6.9%) with tumor recurrence. Among the 10 patients with recurrence, one had CLT and two had HT. Table 2 shows the clinicopathologic and US characteristics of the two groupings. CLT or HT was only found in patients of the female gender. In Grouping 2, the mean age at diagnosis was older in patients without HT (p=0.032). In both groupings, the presence of calcification was more frequently associated with patients with LT (including both CLT and HT) or HT (p=0.041 and 0.047, respectively).

The Kaplan-Meier analysis demonstrated that the presence of LT (both CLT and HT) or HT in PTC patients did not alter the probability of recurrence developing (Fig. 1). To identify predictive factors of recurrence, a Cox proportional hazard model was created. Univariate and multivariate analysis results are listed in Table 3 and 4. On multivariate analysis, neither LT nor HT was an independent predictor of recurrence. Pathologic tumor size and taller than wide shape on US were independent predictors of recurrence in both groupings.

Lymphocytic thyroiditis has a certain pathologic spectrum with various degrees of inflammatory change with lymphocytic infiltration.15 Although a number of investigators have classified LT into several types according to different degrees of lymphocytic infiltration, epithelial changes, and fibrosis (Table 5),15,16,17,18,19,20,21 most pathologists have used CLT and HT. CLT is defined when histologic characteristics meet the following conditions; presence of diffuse lymphocytic infiltrate, oxyphilic cells, and the formation of lymphoid follicles or reactive germinal centers.8 HT has been differentiated from CLT and is defined when histologic characteristics meet the following additional conditions along with the characteristics of CLT; presence of Hurthle cells and varying degree of acini atrophy.22

The nature association between LT and PTC is still uncertain. A molecular study concluded that multiple occult tumors exist in HT at high frequency.23 Some studies suggested that chronic thyroiditis will induce malignant transformation by enhancing mitosis and proliferation of thyroid cells.24 Although its nature remains uncertain, studies regarding the relationship between CLT or HT and PTC have been reported. As HT patients showed a higher incidence of thyroid carcinoma, HT was thought to be a predisposing factor in the development of thyroid carcinoma.25 However, there was a report showing that the pathogenesis of PTC itself stimulates lymphocytic infiltration and the autoimmune mechanism was suggested as a result of malignant pathogenesis rather than as a premalignant factor.26 In fact, CLT and HT have been reported to be favorable factors in the prognosis of PTC,4,7,17,27 although the issue remains somewhat controversial.2,3 The presence of CLT or HT in PTC patients has been related to lower T stage, less extrathyroidal extension, or less nodal metastasis compared to patients without CLT.4,7,17,27 Furthermore, disease free survival was found to be significantly longer in PTC patients with coexisting CLT.8 On the other hand, other studies have shown CLT or HT not affecting any prognostic features such as size, angioinvasion, or multifocality, thereby showing no association between the presence of CLT or HT and PTC aggressiveness.2,3 Although many investigators evaluated the relationship between CLT or HT and the prognostic outcomes of PTC patients, they mixed "CLT" with "HT" and in some cases, even categorized them as the same pathologic condition. Also, to our knowledge, there have been no published reports on the relationship between different pathologic grades of LT and the prognostic outcomes of PTC. Therefore, we sought to investigate whether the pathologic grade of LT can affect the outcome of PTC patients along with other clinicopathologic and US features.

Factors influencing a poor outcome of thyroid tumor recurrence include older age, male gender, larger size, cervical node or distant metastasis, extrathyroidal extension, multiplicity of the tumor, and tumor stage.5,28 In our study, larger PTC is significantly associated with a higher recurrence rate of PTC regardless of the presence of CLT or HT, similar to previous reports that show larger PTC nodules having an association with poor prognostic factors.5,29 There have been several reports about the relationship of US characteristics with clinical outcomes. Patients with PTC with benign looking results on US had better prognosis than ones with malignant looking results on US.30 Ill-defined margins or the presence of calcification was associated with lymph node metastasis in PTC patients.31,32 PTCs with taller-than-wide shape on US were associated with extrathyroidal extension and BRAF mutation which may be a poor prognostic factor.33 Our study shows that a PTC patient with taller-than-wide shape on US is more likely to recur with or without LT. Further studies will be needed to verify this.

There are some limitations to our study. First, this is a retrospective study and has selection bias as we excluded patients with other primary malignancies, with previous history of surgery or other procedures at the thyroid gland, or with a follow-up of less than 5 years. Second, all US image analyses were based on the retrospective review of previously taken images. The interpretation of US findings by the reviewer could have been different from the actual US performer. Third, only one pathologist and radiologist reviewed the specimens and US findings. Therefore, interobserver variability should be considered in future studies. Fourth, there was a relatively small number of the study population to compare disease free survival between each group of patients. Further study is needed with larger number of patients in each group to obtain more profound results.

We conclude that there was no relationship between PTC prognosis and different grades of LT. Pathologic tumor size and taller than wide shape on US were independent predictors of PTC recurrence regardless of concurrent LT.