Differentiation of renal oncocytoma from renal cell carcinoma by means of ⁹⁹Tc-Sestamibi SPECT/CT

Sammanfattning: Purpose: An increasing body of literature indicates the beneficial role of [99m]Tc-Sestamibi SPECT/CT in the non-invasive differentiation of renal oncocytoma (RO) from renal cell carcinoma (RCC). This thesis presents a comprehensive approach of [99m]Tc-Sestamibi SPECT/CT examination following the implementation of quantitative tools in addition to visual assessment. An additional aim is to explain the differences in [99m]Tc-Sestamibi uptake among the different RCC subgroups on histometabolomic grounds. Methods: 57 radiologically detected kidney tumours from 52 patients were included in the present thesis. Each participant underwent a [99m]Tc-Sestamibi SPECT/CT examination before nephrectomy or percutaneous kidney biopsy. Kidney tumours with increased [99m]Tc-Sestamibi uptake were classified as positive (Sestamibi positive). In contrast, those with equal or decreased [99m]Tc-Sestamibi compared to the ipsilateral non-tumoral kidney parenchyma were classified as negative (Sestamibi negative). Following the visual assessment, quantitative SUVmean and SUVmax measurements performed in the examined kidney tumour and the non- tumoral kidney parenchyma that correlated with the histopathological results. Additional immunohistochemical investigation, in situ metabolomics profile characterisation and correlation of mitochondrial content with [99m]Tc-Sestamibi SPECT/CT data, were also performed. Results: Visual assessment of [99m]Tc-Sestamibi SPECT/CT examination resulted in a sensitivity of 82% whereas, the quantitative assessment showed a sensitivity of 64% regarding the preoperative characterisation of RO. [99m]Tc-Sestamibi SPECT/CT identifies a larger Sestamibi-positive tumour group containing RO, hybrid oncocytic chromophobe tumour (HOCT) and the majority of chromophobe RCC (chRCC). A discriminatory metabolomic signature was identified for Sestamibi positive Birt-Hogg-Dubè-associated HOCT vs other renal oncocytic tumours. Metabolomic differences were also found between Sestamibi positive and negative chRCCs. Conclusion: Sestamibi positive kidney tumours on SPECT/CT examination are possibly of benign nature. Quantitative assessment with SUV SPECT measurements did not improve the diagnostic performance of [99m]Tc-Sestamibi SPECT/CT. Sestamibi negative kidney tumours should be considered for surgery due to their possibly malignant nature. On the other hand, Sestamibi positive kidney tumours could be suited for biopsy and/or follow up according to surveillance protocols.