Influenced by the constantly evolving approach to non-invasive patient management in the era of functional imaging, investigators demonstrated the diagnostic potential of DW-MR images and calculated ADC values to differentiate between benign and malignant tumors including those of the mediastinum. Hence, serving as a virtual biopsy and in some cases preventing unnecessary diagnostic intervention.
Conducted studies showed that the ADC values of malignant mediastinal lesions are significantly lower than those of benign lesions and determined cut-off ADC values to differentiate the two.
Taking this a step forward, the main purpose of our prospective study was to investigate the potential of DW-MRI to characterize malignant mediastinal lesions using their ADC values.
The study included 33 patients with a mediastinal mass identified on CT that underwent MRI of the chest with DWI and were later histopathologically diagnosed with a malignant mediastinal lesion. Patients were grouped according to their histopathological diagnosis.
There was no statistically significant difference between the ADCmean values of the histopathological groups of lesions assessed. This is in concordance with the study carried out by Tondo et al., 2011 who found substantial overlap in ADCmean values of all examined malignant lesions (n = 30), namely bronchogenic carcinoma, thymic carcinoma, and malignant teratoma .
Moreover, the 32 malignant mediastinal lesions studied by Nasr et al., 2016 included lymphoma, bronchogenic carcinoma, invasive thymoma, and metastases. No significant difference between their ADCmean values was found as well .
Likewise, the 30 malignant mediastinal tumors in Abdel Razek et al., 2009s study were lymphoma, bronchogenic carcinoma, invasive thymoma, and angiosarcoma and again difference between their ADCmean values was insignificant with evident overlapping of the ADC values of lymphoma, bronchogenic carcinoma, and thymoma .
These findings may be attributed to a relatively small sample size and/or heterogeneity of the histopathological subtypes of malignant mediastinal lesions evaluated.
In agreement with Nasr et al., there was no statistically significant difference between the ADCmean values of lymphoma and the ADCmean values of the rest of the histopathological groups conjointly. Tondo et al., 2011 reported similar results to ours where no significant difference was found between bronchogenic carcinoma (adenocarcinomas) and malignant mediastinal lesions in their study [11, 16].
On comparing the ADCmean values of lymphoma and bronchogenic carcinoma, lesions most frequently encountered in our study, the difference between their ADCmean values was statistically insignificant as well. Among the 26 malignant lesions prospectively studied by Gümüştaş et al., 2011, 11 were bronchogenic carcinoma (NSCLC) and 9 were lymphoma. When their ADCmean values were compared, no significant difference was found with an overlap between these two subgroups; results similar to ours. However, Maeda et al., 2005, Abdel Razek et al., 2006, Sumi et al., 2007, Holzapfel et al., 2009 and Kato et al. 2015 reported that the ADC of lymphoma is significantly lower than that of squamous cell carcinoma of the head and neck [14, 18,19,20,21,22].
Anterior mediastinal lesions “most importantly lymphoma, thymic, and germ cell tumors” in our study were entitled to be evaluated separately and again difference between their ADC values was statistically insignificant. Yabuuchi et al., 2015 conducted a retrospective study in the search of significant parameters to characterize anterior mediastinal tumors; one of the parameters evaluated was tumors’ ADC value. Malignant anterior mediastinal lesions included in their study were thymic epithelial tumors (malignant thymoma and thymic carcinoma), lymphoma, and germ cell tumors. In agreement with our results, there was no significant difference between the ADC of these histopathological subtypes at both initial and validation studies .
Regarding the pathological subtypes of lymphoma; in the retrospective study of mediastinal lymphadenopathy in children by Abdel Razek et al., 2015, the average ADCmean of NHL was lower than that of HD—results similar to ours—but the difference between the two was insignificant. On searching the literature, no attempts at using DWI to differentiate between lymphoma subtypes, in particular, were found .
A meta-analysis of 34 studies (conducted in the years 2007 to 2014) involving 2086 patients with pulmonary lesions was recently performed by Shen et al., 2016. One of their objectives was to evaluate the role of ADC in characterizing subtypes of lung cancer. Pooled ADC values of SCLC were significantly lower than those of NSCLC, which to an extent agrees with our study (results more or less similar to ours). The potential histopathological rationale might be that SCLC has high tumoral cellularity, large nuclei, and almost no cytoplasm, all of which restrict the diffusion of water molecules thereby reducing ADC values .
Limited data are available on quantitative assessment of thymic epithelial tumors (TETs) by using DW-MRI from small cohorts of studies which considered various anterior mediastinal tumors. Not to mention that those studies did not attempt to differentiate thymomas based on WHO and Masaoka-Koga classifications by using ADC. Recently, a study by Abdel Razek et al. involving 30 patients with TETs has demonstrated the ability of ADC in differentiating low-risk from high-risk tumors, and early from advanced disease. Mean ADC values of high-risk thymomas and advanced stage TETs were significantly lower than those of low-risk thymomas and early-stage TETs respectively. They determined cut-off mean ADC values of 1.22 mm2/s and 1.25 mm2/s below which a high-risk thymoma is indicated. In a relatively similar study by Priola et al., accurate cut-off mean ADC values of 1.309 × 10−3 mm2/s and 1.243 × 10−3 mm2/s were determined below which a high-risk thymoma and an advanced stage TET are indicated respectively. Moreover, mean ADC of B3 thymoma was significantly lower than that of B2 thymoma. ADC levels were significantly associated with disease-free survival of patients with a recurrence rate being higher for patients with ADC ≤ 1.299 × 10−3 mm2/s. To conclude, ADC helps to differentiate high-risk from low-risk thymomas and may be used as a prognostic indicator of recurrence, yet further studies are needed to validate these results [26, 27].
Nasr et al., 2016, Usuda et al.,2015, Tondo et al., 2011, Gümüştaş et al., 2011 and Abdel Razek et al., 2009 conducted prospective/retrospective studies to quantitatively assess and differentiate benign and malignant mediastinal lesions using DWI. They determined highly sensitive and specific cut-off ADC values below which a malignant mediastinal lesion is indicated; 1.15 × 10−3, 2.21 × 10−3, 1.25 × 10−3, 1.39 × 10−3, and 1.56 × 10−3 mm2/s respectively. One lesion, namely a malignant teratoma had an ADCmean evidently higher than these cut-off ADC values (ADCmean = 2.44 × 10−3 mm2/s) and was hence mistaken for a benign lesion. This may be explained by the fact that when the mass was surgically excised, it proved malignant only by the presence of microscopic foci of immature neuroepithelial component [11, 13, 14, 16, 17].
The one lesion pathologically diagnosed as an angiosarcoma was overall hemorrhagic in nature with no sizeable non-hemorrhagic soft tissue components seen on the conventional MR images rendering a qualitative assessment of the DWI and ADC measurement not possible. This was based on the fact stated by Qayyum, 2009: blood demonstrates signal characteristics of highly cellular soft tissue lesions; a pitfall readily observed on DWI .
A number of authors recommended that minimum ADC is used instead of mean ADC when quantitatively assessing a lesion since it theoretically reflects the area of highest tumor cellularity and unlike mean ADC, it would not underestimate tumor cellularity in the context of a largely necrotic tumor . Accordingly, a minimum ADC of each lesion was taken into account when attempting to characterize the different malignant mediastinal lesions included in this study. However, the aforementioned results did not differ considerably when minimum ADC was used instead of mean ADC. Nevertheless, most published studies that evaluated mediastinal lesions using DWI referred to mean and not minimum ADC values.