In the present study, estimation of ADC value of RCC was significantly correlated with gender, tumor size, cystic/necrotic features, growth pattern, clinical stage, distant metastasis, histological grade, and unenhanced T1. The prognostic factors of RCC accompanied by significantly low ADC values were male gender, size ≤ 4 cm, solid component, isointense on unenhanced T1, infiltrative growth, cystic/necrotic features, presence of distant metastasis, grade IV, and high-stage (III and IV) RCCs.
A b value of 800 s/mm2 was used in the current study because we had relatively few cases for histopathological analysis and the study was retrospective in type. We did not encompass benign tumor lesions, which narrow the use of ADC values for discriminating malignant from benign tumors. With increasing b values, improved qualitative images with a preferable signal to noise ratio are obtained .
In the current study, with a b value of 800 s/mm2, clear RCC had higher mean ADC values than non-clear RCC.
The previous results varied in their evaluation; although most of them had similar results, few disagreed. Similar results were with Youn et al., who showed high ADC (1.6 × 10−3 mm2/s) for clear RCC compared with ADC for non-clear RCC (1.5 × 10−3 mm2/s) . Sharma et al. found ADC (1.6 × 10−3 mm2/s) with clear RCC and ADC (1 × 10-3 mm2/s) for non-clear RCC . Cheng et al., in a study of 85 RCC, observed that non-clear RCC had significantly lower mean ADC values (1.1 × 10−3 mm2/s) than clear-cell RCC (1.8 × 10−3 mm2/s) . Kim et al. also reported that non-clear-cell RCC had significantly lower mean ADC values (1.6 × 10−3 mm2/s) than clear-cell RCC (1.8 × 10−3 mm2) .
On another side, the results of Paudyal et al. proved that ADC value for clear RCC was lower (1.6 1 × 10−3 mm2/s) than in non-clear RCC (6.72 ± 1.85 × 10-3 mm2/s) .
There is no doubt that evaluation of ADC value depends mainly on the number of cells and the relatively intercellular space which in turn can restrict water movement. Clear RCC tumors are characterized by narrow intercellular space due to presence of large cell and rich cytoplasm, in contrast to non-clear RCC. In the results of Paudyal, although different in appearance, the ADC values largely agreed, and this could be due to the size of samples taken and the nature of the tumors. So, further studies with larger patient populations are warranted .
The number of cells is a crucial indicator of tumor grade . It has been suggested that the decreased ADC value may be due to their increased cellularity, larger nuclei with more abundant macromolecular proteins, and less extracellular space [20, 21].
The present study demonstrated a significant inverse relationship between ADC values and histological grade. Low-grade tumors had higher ADC values than high-grade tumors.
Several studies reported similar results. Youn et al. found that high-grade tumor had lower mean ADC values (1.3 × 10−3 mm2/s) than lower grade tumors (1.7 × 10−3 mm2/s) . Kim et al. also reported that high-grade clear-cell RCC (1.7 × 10−3 mm2/s) was observed to have significantly lower mean ADC values than low-grade clear-cell RCC (2.0 × 10−3 mm2/s) .
On another side, in a study including 57 patients, Rosenkrantz et al. revealed a strong positive correlation of the ADC to grading . Yu et al. reported that there were statistically significant differences in the ADC values of low- and high-grade RCCs . Conversely, Sandrasegaran et al. observed no significant difference in ADC values related to tumor grading .
Heterogeneity of RCC may explain this contradictory data, because some tumor presents areas of different grades, which are often found within the same tumor. Therefore, Gurel et al.  suggested that conventional MRI in addition with ADC was superior to percutaneous biopsy and might improve tissue characterization.
In the current study, there was a statistically significant difference in ADC values between low and high-stage RCCs. RCC accompanied by significantly low ADC values ≤ 1.2 × 10−3 mm2/s is related to the presence of distant metastasis.
Our result agreed with the previous study, which found a statistically significant difference in the ADC values between T1a clear-cell RCC and clear-cell RCC with distant metastasis .
In our study, there was statistically significant positive correlation between the size of RCC and ADC values. There are a limited number of studies focusing on the relation of the size of RCC and the ADC values. In a study of 49 patients, Mitsunari et al. showed a weak significant correlation between the tumor size and ADC value of clear-cell RCC .
In the general role, the size of RCC may not have a role in the determination of RCC aggressiveness but has a role in predicting the nuclear grade of RCC. So, ADC values should be used in conjunction with tumor size as an additional finding.
In the current study, RCC lesion with distant metastasis had statistically significant lower mean ADC values with strong negative correlation. A previous study reported that ADC values of clear RCC may be related to the presence of distant metastasis. Thus, in a clinical situation, clear-cell RCC with low ADC values should be inspected broadly for the risk of distant metastasis .
In our study, we have defined growth pattern as a parameter and analyzed its prognostic usefulness. The infiltrative lesion had low ADC value compared to cortical lesion, in addition to the strong positive correlation noted in between.
Recently, few reports considered that RCC with an infiltrative growth pattern may have more migration capacity than RCC with cortical growth pattern and adopted growth pattern as a parameters for RCC prognosis . Further studies are crucial to approve the convenience of this parameter.
The presence of tumor necrosis is a well-established independent indicator of a poor prognosis for RCC, and presence of necrosis results in higher ADC values [18, 19]. In our study, there was a statistically significant positive correlation between the ADC values and tumor necrosis.
We found a strong negative correlation between ADC values and the tissue component. The solid lesions had statistically significantly lower mean ADC value levels than cystic/necrotic lesions.
The histology of RCC is heterogeneous and contains a lot of variety including necrosis, hemorrhage, debris, and solid tissues which elevate the value of ADC .
In our study, T1 isointense lesions were associated with lower ADC values, and there was a strong negative correlation between ADC values and T1 signal intensity. This result was seen in previously published data . This compatibility might be a result of the homogeneity of the different lesions and the comparison between the same malignant group.
This study has several limitations. Firstly, the study had a retrospective, non-randomized design and single institutional series. Secondly, only one b value (800 mm2/s) was used for the estimation of the ADC. It may be fascinating to get additional b values to obtain more strict ADC data. Thirdly, we did not estimate the reproducibility of the ADC values gathered for RCC.