title: The use of semi-quantitative ultrasound elastosonography in combination with conventional ultrasonography and contrast-enhanced ultrasonography in the assessment of malignancy risk of thyroid nodules with indeterminate cytology.
abstract: BACKGROUND
  The pre-surgical selection of thyroid nodules with indeterminate cytology (Thy 3 according to British Thyroid Association) after fine-needle aspiration biopsy (FNAB) is currently required in order to reduce unnecessary total thyroidectomy. The objective of our study was to use a surgical series of Thy 3 nodules to evaluate the predictive role of ultrasound elastosonography (USE) and contrast-enhanced ultrasonography (CEUS) in pre-surgical diagnoses of malignancy.
  
  
  METHODS
  We enrolled 63 patients with Thy 3 nodules in which cytological-histological correlation was available. The ELX 2/1 strain index was obtained by means of semi-quantitative USE, which was performed before surgery in addition to conventional ultrasonography (US) and contrast-enhanced US (CEUS) on the Thy 3 nodules. The ELX 2/1 strain index, a five-item US score and both peak (P) index and time to peak (TTP) index from CEUS were correlated with the histological results. After surgical diagnosis, the data were analysed by using a receiver-operating characteristic (ROC) curve.
  
  
  RESULTS
  Histology was benign in 50 and malignant in 13 Thy 3 nodules. No difference in maximal diameter was noted between benign (22.8 ± 1.6 mm) and malignant (18.9 ± 2.9 mm) nodules. Significant correlations were found between histology and cumulative US findings (p=0.005), ELX 2/1 index (p=0.002), P index (p=0.01) and TTP index (p=0.02). On analysing data from US, USE and CEUS, significant ROC areas under the curve were observed (p<0.0001). A cut-off value was set for US (>2), ELX 2/1 (>0.95), P index (<0.99) and TTP index (>0.98) scores. The diagnostic power of the cumulative pre-surgical analysis of Thy 3 nodules with US, USE and CEUS, considering the experimental cut-off points obtained from the ROC curves was: sensitivity 64%, specificity 92%, PPV 75% and accuracy 84%.
  
  
  CONCLUSIONS
  The ELX 2/1 index in conjunction with the US score can be useful in orienting surgical strategies in Thy 3 nodules. The information added by CEUS is less sensitive than that provided by US and USE. The use of a cut-off based on histology can reduce thyroidectomy. Observation should be the first choice when not all instrumental results are suspect.
authors.affiliation: Endocrine Unit, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy ; UO Clinica Endocrinologica, Viale Benedetto XV, 6, I-16100 Genoa, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Giusti
authors.affiliation: Endocrine Unit, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Campomenosi
authors.affiliation: Endocrine Unit, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gay
authors.affiliation: Cytopathology and Pathology Unit, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Massa
authors.affiliation: Radiology Unit, Ospedale Evangelico, Genoa, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Silvestri
authors.affiliation: Endocrine Unit, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Monti
authors.affiliation: Radiology Unit, Ospedale Evangelico, Genoa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Turtulici
keywords: Contrast-enhanced ultrasonography; Cytological–histological correlation; Indeterminate cytology; ROC analysis; Strain index; Thyroid nodules; Ultrasosonography; Ultrasound elastosonography