Solitary thyroid nodule is a single swelling in an otherwise normal gland. It is usually a benign lesion [1]. Most of the nodules tend to have a benign nature and the malignancy has been reported in less than 5% of the nodules [2].
The most frequently used methods for assessing thyroid nodules are clinical examination, ultrasound, thyroid scintigraphy (SC), and fine-needle aspiration biopsy (FNAB). There is no single reliable criterion used to separate among benign and malignant nodules [3]. Color Doppler US findings are controversial in terms of malignant nodules [4,5,6,7]. SC gives information about thyroid gland functions [8], however, risks of exposure to radiation and the fact that not all functioning nodules on scintigraphy are benign are major limitations [9,10,11]. Using FNAB, non-conclusive results were observed in 13–30% of patients, and malignancy percentage in this group changes between 10 and 50% [12,13,14].
Conventional MRI of the thyroid gland can give information about the location and size of thyroid lesions but still do not have the specificity for distinguishing benign from malignant nodules [15].
Routine diffusion-weighted MR imaging (DWI) can measure the mobility of water molecules diffusing in tissues which is impacted by biophysical characteristics such as cell density, membrane integrity, and microstructure [16,17,18]. Recently, DWI has been used in differentiating benign and malignant nodules in thyroid gland [19]. Apparent diffusion coefficient (ADC) value is a quantitative parameter for distinguishing malignant from benign thyroid nodule [15].
Reduced ADC values have been reported for most malignant tumors and are thought to be due to cellular membranes impeding the mobility of water protons [19, 20].
In our study, there was a significant difference between the mean ADC value of benign and malignant nodules (P value < 0.0001), the mean ADC of the malignant thyroid nodules (15 nodules) was (0.71 ± 0.15 × 10-3 mm2/s) while that of the benign thyroid nodules (58 nodules) was (1.7 ± 0.12 × 10-3 mm2/s). This was in concordance with the study of El-Hariri et al. [21] who studied 46 patients with 56 thyroid nodules. The mean ADC of the benign thyroid nodules in their results was 1.85 + 0.24 × 10-3 mm2/s, while the mean ADC of the malignant thyroid nodules was 0.89 + 0.27 × 10-3 mm2/s.
The ADC values of malignant thyroid nodules were significantly lower than the ADC values of benign thyroid nodules (P value < 0.0001). A recent study of Elshafey et al. [22] also reported high ADC values (1.78 + 0.21 × 10-3 mm2/s) for benign nodules and lower ADC values (0.59 + 0.24 × 10-3 mm2/s) for malignant nodules, and these were statistically significant (P value < 0.0001).
Using the pathology results as a standard reference, area under ROC curve was found to be 98% for an ADC cutoff value of 0.92 × 10-3 mm2/s that corresponded to an acquisition with b value of 400 s/mm2 with a sensitivity of 97.5%, a specificity of 94.4%, and an accuracy of 99.2%. This cutoff value was conceded with that of Abdel Razek et al. [23], who determined that the ADC value of 0.98 × 10-3 mm2/s was the cutoff value differentiating between benign and malignant thyroid nodules with a sensitivity of 97.5%, a specificity of 91.7%, and an accuracy of 98.9%. In the study of Elshafey et al., the reported cutoff value was 0.8 × 10-3 mm2/s, and this was attributed to the highly cellular adenomatous tissue that shows slight low ADC. Shi et al. found that when the b factor was 500 s/mm2, an ADC value of 1.704 × 10-3mm2/s can be threshold differentiating malignant from benign nodules, with 92% sensitivity, 88% specificity, and 87% accuracy. He clarified that the higher cell density and more severe desmoplastic response were the causes of the lower ADC value of thyroid cancer. A higher cutoff ADC value (2.17 × 10-3 mm2/s) was determined by Wu et al. [15] with sensitivity and specificity of 76.5 and 100%, respectively.
The ADC values of benign thyroid nodule may vary according to the complex composition within the nodule (colloid, tiny necrosis and cystic change, hemorrhage, fibrosis, and calcium). ADC values were highest in thyroid cysts since it contained colloid material made of serous or concentrated thyroglobulin [15].
In our study, and using pathological results, we could not depend on the ADC value in differentiating between different pathological subtypes of thyroid nodules. P value ranged from 0.054 to 0.062 between different pathological subtypes. Adenomatous nodule and follicular adenoma showed ADC values of 1.31–1.92 × 10-3 and 1.23–2 × 10-3, respectively. For malignant nodules, papillary and follicular carcinomas showed ADC values of 0.72–1.32 × 10-3 and 0.61–1.24 × 10-3, respectively. This was in agreement with Abdel Razek et al. who found that there were insignificant differences in the ADC values of the various malignant nodules, with P = 464. Also. in a study done by Schueller-Weidekamm et al., [24] they studied 25 patients with thyroid nodules and stated that there was no statistically significant difference in the ADC values between different pathological subtypes of malignant nodules (P 0.05). These results can be explained by the fact that it is not possible to differentiate the various thyroid gland carcinomas by their specific cell attenuation.
It was suggested that the ADC values of benign thyroid nodule may vary according to the complex composition within the nodule (colloid, tiny necrosis and cystic change, hemorrhage, fibrosis, and calcium) [15], we did not find that much helpful in differentiating between subtypes of benign thyroid nodules. In our study, ADC values were highest in thyroid cysts since it contained colloid cyst made of serous or concentrated thyroglobulin.
Although calcification may lead to a decrease of ADC values in papillary thyroid carcinoma, we also did not find this helpful in differentiating between it and follicular carcinoma.
There are still some limitations in this study. First, the relatively small number (20.5%) of the malignant nodules somehow limits the statistical power. Second, small thyroid nodules less than 10 mm were not included. Improvement in the software of diffusion-weighted MR imaging will help in the detection of smaller lesions in future studies.