Patients with Indeterminate Thyroid Nodules at Cytology and Cancer at Histology Have a More Favorable Outcome Compared with Patients with Suspicious or Malignant Cytology.

BACKGROUND: The outcomes of patients with thyroid cancer proven by histology in patients in whom cytology was Thy 3 (indeterminate; Thy 3 patients in this study) based on the Italian consensus classification compared with those in whom cytology was Thy 4 (suspicious for malignancy) or Thy 5 (indicative for malignancy) (Thy 4-5 patients here) remains unclear. OBJECTIVE: To analyze the outcome of 371 Thy 3 patients versus 269 Thy 4-5 patients homogeneously treated with total thyroidectomy and 131I activity. RESULTS: T1 stage was observed in 46.0% of Thy 3 and in 38.8% of Thy 4-5 patients (p = 0.02), N0 in 95.9% of Thy 3 and in 75.5% of Thy 4-5 patients (p < 0.0001). 35/261 (9.6%) Thy 3 and 85/269 (31.5%) Thy 4-5 patients required >30 mCi of 131I (p < 0.0001). 359/371 (96.8%) Thy 3 and 232/269 (86.2%) Thy 4-5 patients were free of disease at the end of follow-up (p < 0.001). The time required to obtain 50% of patients in remission was 2 years in Thy 3 and 4 years in Thy 4-5 patients (p < 0.001). The most common histological type was the follicular variant of papillary thyroid carcinoma (FV-PTC) in Thy 3 patients (239/371, 64.4%) and the classic variant in Thy 4-5 patients (185/269; 68.8%). The FV-PTC had better prognostic features compared with the other PTC variants: T1 stage was observed in 133/277 (48.0%) FV-PTC patients and in 146/363 (40.0%) patients with the other variants (p < 0.001), N0 was present in 265/277 (96.0%) FV-PTC and in 290/363 (79.8%) patients with the other variants (p < 0.001). Overall, 267/277 FV-PTC patients (96.4%) and 324/363 patients (89.0%) with the other variants were free of disease (p < 0.0008) at the end of follow-up, and the time required to obtain 50% of patients in remission was 2 years in FV-PTC and 4.0 years in the other variants (p < 0.001). CONCLUSION: Patients with Thy 3 cytology have better outcomes of thyroid cancer compared with patients with Thy 4 or Thy 5 cytology, and indeterminate cytology is commonly associated with the less aggressive FV-PTC.

Low Elasticity of Thyroid Nodules on Ultrasound Elastography Is Correlated with Malignancy, Degree of Fibrosis, and High Expression of Galectin-3 and Fibronectin-1.

BACKGROUND: Thyroid ultrasound (US) elastography provides an estimation of tissue stiffness and is helpful to differentiate malignant from benign lesions. Tissue proprieties and molecules causing stiffness are not established. The aim of the study was to correlate US elastography findings with tissue properties in thyroid nodules. METHODS: A total of 115 thyroid nodules from 112 patients who underwent surgery for the presence of Thy 3 (indeterminate) cytology (n = 67), Thy 4-5 (suspicious-indicative of carcinoma) cytology (n = 47), or large goiter in the presence of Thy 2 cytology (n = 1) and suspicious US features were examined by US elastography. Tissues obtained after surgery were characterized for cell number, microvessel density, fibrosis, and expression of galectin-3 (Gal-3) and fibronectin-1 (FN-1). RESULTS: Low elasticity on qualitative US elastography (LoEl) was found in 66 nodules (one benign and 65 carcinomas); high elasticity (HiEl) was found in 49 nodules (46 benign and three carcinomas; p < 0.0001). Quantitative analysis, performed in 24 nodules and expressed as elastic ratio between the strain of the nodule and that of the surrounding thyroid parenchyma, showed a mean of 1.90 (interquartile range [IQR] 1.18-2.77) in 14 nodules with LoEl, and a mean of 1.01 (IQR 0.91-1.10) in 10 nodules with HiEl (p = 0.002). Stiffness did not correlate with cell number and was inversely correlated with microvessel density. Fibrosis was higher in nodules with LoEl than in those with HiEl (p = 0.009) and in carcinomas than in benign nodules (p = 0.02). Fibrosis was higher in nodules with high expression of Gal-3 (p < 0.001) and FN-1 (p = 0.004). Fibrosis and expression of Gal-3 and FN-1 were higher in the classic compared with the follicular variant of papillary thyroid carcinoma and lower in follicular adenomas. CONCLUSIONS: Low elasticity at US elastography is highly correlated with malignancy. Nodule stiffness is correlated with fibrosis and expression of Gal-3 and FN-1. These features are more evident in the classic than in the follicular variant of papillary thyroid carcinoma.

The large majority of 1520 patients with indeterminate thyroid nodule at cytology have a favorable outcome, and a clinical risk score has a high negative predictive value for a more cumbersome cancer disease.

CONTEXT: Clinical management of patients with thyroid nodules indeterminate at fine-needle aspiration (FNA) cytology is still unsettled. OBJECTIVE: Our objective was to establish the clinical outcome of patients with thyroid nodules indeterminate at cytology and to identify the features associated with malignancy. DESIGN AND PATIENTS: This was a retrospective evaluation of 1520 consecutive patients with indeterminate cytology among 100 065 patients who underwent FNA between January 2000 and December 2010. RESULTS: Of 1520 patients, 371 (24.4 %) had thyroid cancer at histology, the follicular variant of papillary cancer being the most frequent histotype, and 342 patients with cancer were free of disease after thyroidectomy and (131)I remnant ablation, whereas 29 needed further treatment because of persistent disease. Among them, only 12 had persistence of disease at the end of follow-up. Atypias at cytology (P = .001), blurred nodule margins (P = .005), and spot microcalcifications (P = .003) at thyroid ultrasound (US) were significantly associated with malignancy. A clinical score including cytology and US characteristics was calculated; the lowest value showed a high negative predictive value (83.9%) for the presence of malignancy and even higher (99.5%) for the presence of a more cumbersome cancer disease, and only 4 of the 29 patients who needed further treatment were included in the group with the lowest risk score. CONCLUSIONS: Patients with Thy 3 cytology and histology of thyroid cancer had an overall good prognosis. A clinical risk score including the results of cytology and US features is helpful in the management of patients with indeterminate thyroid nodules.