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

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 11C-methionine uptake on PET. From December 2009 to October 2010, we performed stereotactic biopsies in 12 patients with radiologically heterogeneous, ring-enhanced 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 11C-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 glio-blastoma. 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 11C-methionine uptake mostly reflected cell densities depending on the degree of necrosis.