We investigated the relation between the value of SUV on 18F-FDG PET/CT imaging and the histopathological findings of suspected IgG4-RD-involved lesions. To avoid unnecessary biopsies and to select suitable lesions for biopsy in diseases with multi-organ involvement such as IgG4-RD, determining which lesion is suspected to be disease-involved using a non-invasive test is important. The results of this study indicated that the value of SUVmean, not SUVmax, has good diagnostic performance in IgG4-RD.
In IgG4-RD, 18F-FDG PET/CT has been reported to be more accurate and more sensitive for detecting the lesions associated with IgG4-RD as compared to other imaging techniques. Zhang et al. reported 18F-FDG uptake in multiple organs in 34 of 35 IgG4-RD patients, and 18F-FDG PET/CT imaging was able to detect more organ involvements in 25 of 35 patients as compared to conventional evaluations including ultrasonography and conventional CT12.
Another report revealed that all 21 IgG4-RD patients who underwent 18F-FDG PET/CT presented 18F-FDG uptake in typical IgG4-RD localizations, and some of these lesions were not detected by conventional CT, magnetic resonance imaging, or ultrasound10. Moreover, the correlation of disease activity and 18F-FDG PET/CT has also been reported 10,13,14. 18F-FDG uptake was seen in all patients enrolled in our present study, and several lesions with 18F-FDG uptake were not detected by other imaging modalities (data not shown). Based on these previous studies, we further analyzed whether the characteristics of the region of interest (ROI) of 18F-FDG PET/CT imaging correlated with true lesions of IgG4-RD by comparing them with histopathology.
To analyze the characteristics of suspected IgG4-RD-involved lesions, quantitative analysis was performed. Additionally, to identify the optimal quantitative method for IgG4-RD, we also performed three methods of quantitative analysis. The optimal method for the quantification of PET/CT imaging might be different depending on the disease. For the differentiation of metastatic lesions of non-small-cell lung carcinoma from benign lymph nodes, the SUVmax-lymph node/ SUVmax-primary tumor ratio showed better diagnostic performance as compared to SUVmax-lymph node 19,20. Another study showed that the median SUV was correlated with local recurrence of a squamous cell carcinoma of the anal canal but that SUVmean was not correlated with local recurrence21. In patients with head-and-neck cancer, SUVmean, not SUVmax, was correlated with disease-free survival, and so SUVmean seemed to have the potential to become a prognostic factor in head-and-neck cancer22. Our present study showed that SUVmean and SUVmean/liver were significantly correlated with biopsy-proven IgG4-RD involvement, but that SUVmax was not correlated. This is consistent with the results of other studies. Zhan et al. reported that diffusely elevated 18F-FDG uptake in organs should be considered to be more likely to indicate IgG4-RD lesions as compared to a patchy/nodule uptake pattern12. Diffused and enlarged tissues/organs are clinicopathologic characteristics of IgG4-RD 23,24, such as in the following examples: 1) diffuse infiltration of sinonasal mucosa with an IgG4-positive plasmacytic infiltrate in IgG4-reralted chronic rhinosinusitis; 2) diffusely thickened gastric mucosa on endoscopy in IgG4-related gastritis; 3) diffusely enlarged sausage-shaped pancreas in autoimmune pancreatitis (considered to be on the IgG4-RD spectrum); 4) homogenous thyroid grand enlargement in IgG4-related thyroiditis; and 5) diffuse kidney enlargement and diffuse immune complex deposition in the tubular basement membrane in IgG4-relatad kidney disease. These characteristics are also consistent with our study; namely, the comparison of SUVmean between tissues with abundant IgG4-positive plasmacytes and tissues with few/no IgG4-positive plasmacytes in our study showed more significant differences as compared to the analysis of SUVmax. SUVmax is the most commonly used 18F-FDG PET/CT parameter in daily clinical practice, and it is often included in imaging reports. It is simple and quick to measure, but SUVmax may not represent the status of ROI in IgG4-RD because its value is taken from a single voxel. SUVmean within an ROI is supposed to represent disease status in IgG4-RD more precisely, as we found in this study; therefore, we should calculate SUVmean to identify IgG4-RD lesions. Furthermore, according to ROC curve analysis, the AUC using the value of SUVmean/liver was higher as compared to that using the value of SUVmean. This suggested that SUVmean was influenced by the individual hepatic metabolism, and SUVmean/liver might be more preferable.
ROC curve analysis also indicated SUVmean=4.07 or SUVmean/liver = 1.66 as the cut-off value that discriminated IgG4-RD-associated lesions. This value might be useful for selecting appropriate tissue for biopsy among multiple lesions that are suspected to be associated with IgG4-RD by 18F-FDG uptake or to determine if an 18F-FDG uptake lesion on which a biopsy cannot be performed is an IgG4-RD-associated lesion. However, this cut-off value should be interpreted with caution because the appropriate cut-off value might be different in each organ. For example, the SUVs in the prostate and pancreas were relatively low in our study, although the SUV values of those organs have been reported to be almost the same in normal subjects as compared to other organs25,26. The appropriate cut-off value for each organ should be identified by analyzing a larger number of patients in the future.
Several limitations of this study must be mentioned. The number of patients was small, and the longitudinal analysis was not fully performed. We could evaluate the clinical course for one year in 11 out of 21 patients, but there were no relapses or progression of disease. We therefore could not compare the value of 18F-FDG PET/CT at baseline with respect to the treatment response or disease progression. To make PET/CT imaging more useful for the management of treatment for IgG4-RD, analysis of the relation of the SUV value with the treatment course such as an inadequate response to steroid treatment, the rate of relapse and concomitant use of immunosuppressant desistance is needed in a larger longitudinal study. The values of SUVmean of lymph node were relatively higher as compared to other tissues, and all histopathologic findings of lymph nodes were histopathology-positive in our present study. These results influenced the cut-off value in this study. The value of SUVmean of histopathology-negative lymph node should be compared with that of histopathology-positive lymph node, and mentioned above in the discussion section, further analysis is needed of the cut-off value of SUVmean focused on each organ using larger samples. Also, comparison of the SUVmean of IgG4-RD with those of other diseases such as malignant lymphoma was not done in this study. The utility of the quantification of PET/CT for differentiating IgG4-RD from other diseases should be assessed in a future study.