Predictivity of clinical, laboratory and imaging findings in diagnostic definition of palpable thyroid nodules. A multicenter prospective study

Purpose: To assess the role of clinical, biochemical, and morphological parameters, as added to cytology, for improving pre-surgical diagnosis of palpable thyroid nodules. Methods: Patients with a palpable thyroid nodule were eligible if surgical intervention was indicated after a positive or suspicious for malignancy FNAC (TIR 4–5 according to the 2007 Italian SIAPEC-IAP classification), or two inconclusive FNAC at a ≥3 months interval, or a negative FNAC associated with one or more risk factor. Reference standard was histological malignancy diagnosis. Likelihood ratios of malignancy, sensitivity, specificity, negative (NPV), and positive predictive value (PPV) were described. Multiple correspondence analysis (MCA) and logistic regression were applied. Results: Cancer was found in 433/902 (48%) patients. Considering TIR4–5 only as positive cytology, specificity, and PPV were high (94 and 91%) but sensitivity and NPV were low (61 and 72%); conversely, including TIR3 among positive, sensitivity and NPV were higher (88 and 82%) while specificity and PPV decreased (52 and 63%). Ultrasonographic size ≥3 cm was independently associated with benignity among TIR2 cases (OR of malignancy 0.37, 95% CI 0.18–0.78). In TIR3 cases the hard consistency of small nodules was associated with malignity (OR: 3.51, 95% CI 1.84–6.70, p < 0.001), while size alone, irrespective of consistency, was not diagnostically informative. No other significant association was found in TIR2 and TIR3. Conclusions: The combination of cytology with clinical and ultrasonographic parameters may improve diagnostic definition of palpable thyroid nodules. However, the need for innovative diagnostic tools is still high.