Neurosurgery research fellow Barrow Neurological Institute Phoenix, Arizona, United States
Introduction: Identification of anaplastic regions during non-enhancing glioma surgery is crucial for avoiding histopathological undergrading and defining correct adjuvant treatment. Confocal laser microscopy (CLE) system is a handheld sodium fluorescein-based imaging technology for real-time intraoperative visualization of cellular-level tissue histoarchitecture. We assessed feasibility of CLE for intraoperative real-time in vivo prediction of tumor grade in diffuse gliomas that are not contrast-enhancing on MRI.
Methods: We retrospectively reviewed all patients with non-enhancing gliomas who underwent intraoperative in vivo CLE imaging between 2010 and 2022 years. CLE images were assessed by the CLE-experienced neuropathologist. Identification of histopathological features of glioma atypia (hypercellularity, necrosis, vascular proliferation, cellular pleomorphism) were used as predictors of malignancy. Mildly cellular regions without definitive pleomorphism were regarded as signs of low-grade tumors. Interpretations of CLE images were further compared descriptively and quantitatively to corresponding permanent histology sections.
Results: 2495 CLE images from 26 optical biopsies were obtained on 11 patients (7 male; 4 female; mean age 53.3 years). Permanent histology identified 9 astrocytomas and oligodendrogliomas (3 WHO grade III, and 6 WHO II grade tumors); 1 dysembryoplastic neuroepithelial tumor and 1 fibrovascular lesion. Hypercellularity and pleomorphism were identified in 7 CLE optical biopsies. Hypocellular regions without pleomorphism was identified in 15 CLE optical biopsies. Diagnostic accuracy, sensitivity and specificity of CLE for predicting tumor grade were 86%, 71% (95%CI: 0.36-0.95), and 93% (95%CI: 0.69-0.99), respectively. Positive and negative predictive values were 83% and 87%, respectively.
Conclusion : CLE imaging allows intraoperative identification of histopathological features consistent with regions of various degrees of atypia according to WHO criteria. CLE provides immediate optical biopsy interrogation of brain tissue histoarchitecture without the need to extract and process tissue samples. Intraoperative in vivo utilization of CLE may significantly optimize tissue sampling during surgery of non-enhancing gliomas for precise histopathological diagnosis with an impact on the overall prognosis.
