How to identify a grade 2 diffuse tumor during surgery?

Identifying Grade 2 Diffuse Gliomas During Surgery

Grade 2 diffuse gliomas cannot be reliably distinguished from normal brain by visual inspection alone during surgery, requiring intraoperative neuronavigation based on high-resolution preoperative MRI (1×1×1 mm³) with T2-weighted and contrast-enhanced T1-weighted sequences to guide tissue identification and sampling. 1

Preoperative Imaging Requirements for Intraoperative Identification

Minimum preoperative MRI datasets must include:

• T2-weighted sequences showing grade 2 gliomas as hyperintense lesions 1
• Contrast-enhanced T1-weighted sequences, though grade 2 IDH-mutant gliomas characteristically show little or no contrast enhancement 1
• FLAIR sequences for additional tumor morphology assessment 1

The critical limitation is that morphological visual distinction between tumor and normal brain is not possible during surgery, making image-guided navigation essential 1

Intraoperative Navigation Strategy

Use intraoperative neuronavigation with high-resolution preoperative MRI (1×1×1 mm³) to:

• Localize the non-contrast-enhancing tumor portions visible on T2/FLAIR sequences 1
• Document sampling positions electronically with the navigation system 1
• Obtain samples early during resection (before significant brain shift occurs) to maintain navigational accuracy 1

Key technical point: Anatomical distortions from brain shift violate the rigid body assumption of neuronavigation, so tissue sampling should occur early in the procedure 1

Intraoperative Ultrasound as Adjunct

Navigated intraoperative ultrasound (nioUS) provides real-time tumor visualization:

• Grade 2 gliomas appear hyperechoic (bright) on ultrasound 2
• Approximately 75% of low-grade gliomas show well-defined margins with distinct borders on ultrasound 2
• Ultrasound volumes correlate nearly perfectly with MRI measurements (R² = 0.97) for highly visible tumors 3
• Ultrasound can identify infiltrating tumor beyond T1-defined margins and differentiate solid tumor from T2-visible edema 4

Practical limitation: Tumors previously operated on may have poorly defined ultrasound borders (62% in one series) 2

Tissue Sampling Algorithm for Grade 2 Gliomas

Sample from each MRI-visible tumor portion:

• The non-contrast-enhancing tumor portion (the primary component in grade 2 gliomas) 1
• The surrounding T2/FLAIR hyperintense region 1
• When feasible, immediately adjacent macroscopically normal-appearing parenchyma 1

For spatial heterogeneity assessment:

• Obtain at least two samples per MRI abnormality from opposing regions as distant from each other as possible 1
• Use minimal cauterization to preserve sample viability 1

Critical Pitfalls to Avoid

Brain infiltration extends beyond MRI-visible borders into parenchyma that appears morphologically normal on all imaging sequences, including intraoperatively 1, 5

Non-contrast-enhancing tissue with high cellularity may appear less hyperintense (hypointense or isointense to CSF) on T2/FLAIR compared to surrounding edema, potentially causing confusion 5

Post-treatment cases require extreme caution as therapy-induced changes can mimic tumor on conventional MRI, affecting intraoperative identification 1, 5

Intraoperative Confirmation Strategy

Frozen section analysis with immunohistochemistry:

• Use IDH1 R132H mutant-specific antibody for rapid intraoperative confirmation of IDH-mutant status (the most common molecular signature in grade 2 diffuse gliomas) 1
• Prepare high-quality cytology preparations and frozen sections for accurate intraoperative diagnosis 1

Advanced intraoperative imaging when available:

• Intraoperative MRI can update navigation and adjust for brain shift during later resection stages 1, 6
• Navigated 3D ultrasound provides real-time anatomical updates 1