High Ki-67 index in fine needle aspiration cytology of follicular thyroid tumors is associated with increased risk of carcinoma.

PURPOSE

Preoperative distinction of follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA) is a diagnostic challenge. Our aim was to investigate whether the Ki-67 proliferation index in fine needle aspiration material can contribute to the diagnosis of FTC.

METHODS

We analyzed retrospectively cytological Ki-67 index determined in routine clinical setting and clinical data for 61 patients with FTC, 158 patients with FTA and 15 patients with follicular tumor of uncertain malignant potential (FT-UMP) surgically treated and diagnosed by histopathology at Karolinska University Hospital 2006-2017 (Cohort A). A previously published cohort of 109 patients with follicular tumors was re-analyzed as well (Cohort B).

RESULTS

In Cohort A, patients with FTC had a higher Ki-67 index (p < 0.001), larger tumor size (p < 0.001) and higher age at diagnosis (p = 0.036) compared to patients with FTA or FT-UMP. Hürthle cell differentiation, present in 50 FTA, 20 FTC and 8 FT-UMP, was associated with higher Ki-67 index (p = 0.009). Multivariate analysis of Cohort A identified a high Ki-67 index (odds ratio [OR]: 1.215, p < 0.001) and large tumor size (OR: 1.038, p < 0.001) as independent predictors of FTC. Results remained consistent after exclusion of Hürthle cell tumors and in pooled analysis of Cohort A + B. The area under curve of the Ki-67 index for predicting FTC was 0.722 and a cut-off for Ki-67 index at above 5% resulted in a specificity at 93% and sensitivity at 31%. Subgroup analysis of FTCs in Cohort A showed an association of higher Ki-67 index to extrathyroidal extension (p = 0.001) as well as widely invasive subtype (p = 0.019) based on the WHO 2017 classification.

CONCLUSIONS

Pre-operative Ki-67 index may add diagnostic information for a subset of patients with follicular thyroid tumors.