Outcome and diagnostic reproducibility of the thyroid cytology "indeterminate categories" SIAPEC/SIE 2014 in a consecutive series of 302 cases

Purpose The clinical impact of the SIAPEC/SIE 2014 classification for thyroid cytology has been addressed in few studies that evaluated the malignancy rate and the relative prevalence of each category. No study analyzed its intra-observer and inter-observer reproducibility, so far. Methods We retrospectively collected all "indeterminate" lesions diagnosed before (2011-2014) and after (2015-2018) the application of the SIAPEC/SIE 2014 classification at our Institution. Their relative malignancy risks were calculated based on available histological diagnoses. Cytological and clinical features of TIR3A were compared with the surgical outcome. Finally, a large set of samples was re-evaluated in blind of the original cytological and histological diagnoses by two pathologists, independently. Results The prevalence of "indeterminate" diagnoses increased in years 2015-2018 (302/1482, 21% with 14% of TIR3A and 7% TIR3B categories) compared to years 2011-2014 (261/1680, 16%). Surgery was performed in 27% TIR3A and in 97% TIR3B cases. Malignancy rates were 40% for TIR3B and 17% for TIR3A, but were greatly influenced by the adoption of the WHO 2017 re-classification of encapsulated follicular-patterned lesions (decreasing to 28% and 6%, respectively). No criteria except for tumor size were associated to malignancy in TIR3A category. Intra-observer agreement of the experienced pathologist was 122/141 (86%), whereas inter-observer agreement between the expert and in-training pathologist was 95/141 (67%). Conclusions In this real-life experience, the sub-classification of TIR3A and TIR3B slightly increased the overall prevalence of "indeterminate" diagnoses. Malignancy rates were higher than estimated for both TIR3A and TIR3B categories. Agreement among observers highly depended on pathologist's training.