Histology of the pleural rind at [F]FDG PET/CT hot and cold spots in mesothelioma patients after talc pleurodesis and neoadjuvant chemotherapy.

The role of 2-deoxy-2-[F]fluoro-D-glucose positron emission tomography/computed tomography ([F]FDG PET/CT) in evaluating induction chemotherapy in pleural mesothelioma (PM) patients is debated. We compared histology at tumor sites with high versus low [F]FDG uptake in order to define a morphologic correlate for persistent metabolic activity. Twenty PM patients with talc pleurodesis and induction chemotherapy followed by extrapleural pleuro-pneumonectomy (EPP, n = 17) or tumor debulking (n = 3) were included. All patients received a PET/CT scan prior to surgery. Orthogonal tissue sections of pleural rind (n total=86) were taken at areas of maximum standardized uptake value (SUV, n = 53) and of low [F]FDG uptake (n = 33) and scored on hematoxylin-eosin and immunohistochemical stainings. Total metabolic activity was scored semiquantitatively. Mean SUV of hot and cold spots correlated with total metabolic activity per patient, but no correlation was found with ypT and tumor cells were present in both hot and cold areas. SUV of only hot spots and cold versus hot spots as well as cold versus hot patients correlated with increased thickness of total pleural rind and fibrosis reaction, but not thickness of vital tumor cells or giant cell reaction. They further correlated with increased expression of glucose transporter 1 (GLUT1) in giant cells but not mesothelioma amount, density, vitality or vascularization. Biphasic histology was associated with SUV in only hot spots and higher total metabolic activity (all p-values <0.05). Interpretation of [F]FDG PET/CT in PM patients is difficult after talc pleurodesis and induction chemotherapy. High glucose turnover is mostly related to fibro-inflammatory remodeling of the pleural rind and GLUT1 transporter expression in giant cells. Response assessment using this technology should only be done to assess extra-thoracic lesions.