Pathologic analysis of glioblastoma via multiple stereotactic biopsies of active tumor and necrosis

Abstract

Abstract.To obtain more representative biopsy specimens in glioblastoma, we performed multiple stereotactic biopsies of active tumor and necrosis. We investigated their pathologic differences of diagnosis and also examined the pathologic features that varied with 11 C-methionine uptake on PET. From December 2009 to October 2010, we performed stereotactic biopsies in 12 patients with radiologically heterogeneous, ringenhanced lesions. We biopsied the MR enhanced lesions for active tumor and the MR non-enhanced lesions for necrosis and analyzed differences of pathologic diagnoses between them. As correlating factors of the degree of 11 C-methionine uptake (T/N ratio), the pathologic findings, including cell density, Ki-67 LI, microvessel density, number of endothelial proliferations, the immunopositivity for L-amino acid transporter 1 (LAT1) were analyzed. The final diagnosis of each specimen was glioblastoma. The diagnostic failure rate was 33.3% (4/12 patients) when we selected only active tumors and 40% (4/10 patients) when we selected necrotic lesions. The T/N ratio showed a statistical correlation with cell density depending on the degree of necrosis and LAT1 immunopositivity (P=0.002 and 0.032). LAT1 was localized in the tumor cells, vascular endothelium, and the vicinity of endothelial proliferation. Multiple stereotactic biopsies of active tumor and necrosis could provide the diagnostic yield in glioblastoma. The 11 C-methionine uptake mostly reflected cell densities depending on the degree of necrosis. IntroductionStereotactic brain biopsy is a minimally invasive form of diagnostic technique that uses a three-dimensional coordinate system to locate small targets inside the brain. Magnetic resonance imaging (MRI) provides sharp anatomical details of the pathologic brain and stereotactic operations generally use MRI. However, an inaccurate diagnosis or underestimation of a lesion's pathological grade sometimes occur because clinicians can get only a small amount of tissue to represent the lesion's total features (1-3). Even if the clinician has a provisional radiological diagnosis of high-grade glioma, the pathologist may confirm a low-grade glioma from the small specimen. Gliomas, especially, are histologically heterogeneous, and inadequate localization of the stereotactic biopsy may produce specimens that are irrelevant for identifying and grading the lesions (4). Endothelial proliferation and/or necrosis are essential diagnostic features for the pathological diagnosis of glioblastoma. On enhanced MR images, an enhanced lesion corresponds to a cellular, highly vascularized area of the neoplasm and a non-enhanced lesion corresponds to a necrotic or cystic lesion, with decreased vasculature (5). Therefore, to obtain more representative biopsy specimens, we biopsied the MR enhanced lesions for active tumor and the MR non-enhanced lesions for necrosis to cover the important pathologic features and investigated their pathologic differences of diagnosis. 11C-methionine uptake is regulated by an amino acid trans...

Glioblastoma Exhibits Inter-Individual Heterogeneity of TSPO and LAT1 Expression in Neoplastic and Parenchymal Cells

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Dose-painted volumetric modulated arc therapy of high-grade glioma using 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine positron emission tomography

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Direct Comparison Between Diffusion-Weighted Mri and Pet/Ct With [11с]methionine in Patients With Cerebral Gliomas

“…Однако существуют иные результаты, указывающие, что основной вклад в повышенное накопление [ 11 С]метионина вносит плотность клеток опухоли. При изучении взаимосвязи между интенсивностью захвата [ 11 С]метионином в глиомах и патогистологическими находками, включая плотность опухолевых клеток, плотность микрососудов, пролиферацию эндотелия сосудов, а также иммунореактивность LAT1, установлена сильная достоверная корреляция между ИН [ 11 С]метионина и плотностью клеток опухоли, но не с площадью микрососудов [25][26][27].…”