Journal of Endocrinological Investigation

, Volume 41, Issue 5, pp 531–538 | Cite as

Evaluation of the Italian cytological subclassification of thyroid indeterminate nodules into TIR-3A and TIR-3B: a retrospective study of 290 cases with histological correlation from a single institution

  • E. Rullo
  • G. Minelli
  • D. Bosco
  • F. Nardi
  • V. Ascoli
Original Article



The Italian consensus to classify thyroid cytology has provided a standardized reporting scheme, including the subdivision of indeterminate for malignancy TIR-3 category into TIR-3A (low-risk) and TIR-3B (high-risk). We aimed to present our experience on this subclassification by evaluating risks of malignancy and the validity in sorting nodules with dissimilar risks. Another aim was to compare our performance against the Bethesda system.


Fine-needle aspirates of 290 TIR-3 that underwent thyroid surgery at our hospital (2008–2013) were reviewed and divided into TIR-3A or TIR-3B, and AUS/FLUS or FN/SFN. Cytological diagnoses were then correlated to histology. Results were evaluated using univariate analysis.


The subclassification into TIR-3A and TIR-3B differentiated hyperplastic nodules (p = 0.000) but not adenomas (p = 0.090). Rates of malignancy were significantly different between TIR-3A (10.2%) and TIR-3B (43.8%); TIR-3B malignancies were often papillary carcinomas (83%). TIR-3A/TIR-3B accounted for high sensitivity (84.5%; CI 79.7–88.4%), accuracy (64.1%; CI 58.6–69.6%) and NPV (89.8%; CI 85.6–93.0%) as opposed to modest specificity (55.8%; CI 49.9–61.6%) and PPV (43.8%; CI 38.1–49.8%). The rate of malignancy in AUS-FLUS was higher than in TIR-3A (p = 0.007), whereas it was not different between FN/SFN and TIR-3B (p = 0.337). Sensitivity of the Bethesda system was significantly lower respect to the Italian system.


The study supports the Italian consensus showing a different risk of malignancy for TIR-3A as compared to TIR-3B. TIR-3A/TIR-3B subclassification is valid to sort out benign nodules (high NPV) and malignancies (high sensitivity) but not adenomas (modest specificity, low PPV). In our experience, sensitivity is the main difference between Italian and Bethesda systems.


Thyroid cancer Thyroid nodule Indeterminate fine-needle aspiration cytology Classification 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

For this type of study, archival material was used so that formal consent is not required. The study was designated as exempt by the ethics committee due to its retrospective nature; moreover, no protected health information was used.

Informed consent

Consent to submit the article has been received explicitly from all co-authors, as well as from the responsible authorities at the institute/organization where the work has been carried out.


No funding sources were received/used for this study.


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Copyright information

© Italian Society of Endocrinology (SIE) 2017

Authors and Affiliations

  1. 1.Dipartimento di Scienze Radiologiche, Oncologiche e Anatomo-PatologicheUniversità SapienzaRomeItaly
  2. 2.Unità di StatisticaIstituto Superiore di SanitàRomeItaly

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