CNS tumor
Diffuse astrocytic and oligodendroglial tumors
Glioblastoma, NOS
Author: Eman Abdelzaher, M.D., Ph.D.
Topic Completed: 1 March 2012
Minor changes: 7 August 2020
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: Glioblastoma [title] NOS
Table of Contents
Definition / general | Sites | Clinical features | Radiology description | Radiology images | Case reports | Gross description | Gross images | Microscopic (histologic) description | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosisCite this page: Abdelzaher E. Glioblastoma, NOS. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumorglioblastoma.html. Accessed January 17th, 2021.
Definition / general
- See glioblastoma-IDH wildtype and glioblastoma-IDH mutant
- NOS (not otherwise specified) suffix was introduced in the 2016 WHO classification for cases in which molecular information is not available or is insufficient for a more specific diagnosis (Louis: WHO Classification of Tumours of the Central Nervous System, 4th Edition, 2016)
- Since this entity definition requires the presence of both IDH mutation and 1p / 19q codeletion, NOS can be used whenever one or both are not known, in a tumor that morphologically shows classical features of glioblastoma
- A subsequent consensus paper from a group of experts named cIMPACT-NOW clarifies that this NOS designation should be used only when results are not available (i.e. they cannot or will not be performed or they were performed but results were not obtainable after a technical failure) and not when testing was performed but did not show the typical or expected alterations (Acta Neuropathol 2018;135:481)
- A detailed report describing the histological and molecular findings should always be provided when using this terminology
- Given the uncertainty of the term NOS, which presents the treating physicians with challenges in deciding adequate treatment, the recommendation is to avoid its use and to seek as much precision as possible in the diagnosis of brain tumors
Sites
- Usually supratentorial; uncommon in cerebellum, rare in spinal cord
- Glioblastoma of brain stem is infrequent and often affects children
Clinical features
- 12 - 15% of adult intracranial tumors, 50 - 60% of astrocytic neoplasms
- Either primary (denovo, without recognizable precursor lesions, with p53 mutation) or secondary (develops slowly from grade II or III astrocytoma, often with partial #10 deletion)
- May be under graded on small stereotactic biopsies due to regional heterogeneity
- Median survival is 1 year; 5 year survival < 5%; survival may be overstated due to low grade tumors that dedifferentiate to glioblastoma (Cancer 2003;98:1745)
- Small cell morphology: associated with worse prognosis; poor prognosis even without necrosis or microvascular proliferation; typically have glioblastoma genetic features
Radiology description
- Contrast enhancing (ring pattern is characteristic), large, surrounded by peritumoral edema, mass effect
Radiology images
Images hosted on other servers:
MRI sagittal view
With ring enhancement
Case reports
- Cerebellar tumor presenting as gliomatosis cerebri that transformed to glioblastoma (J Neurosurg 2005;102:72)
Gross description
- Fast growing tumors may have apparent pseudocapsule
- Large tumors are poorly delineated
- Usually solitary but may cross midline through corpus callosum, massa intermedia or anterior commissure to produce a "butterfly" lesion
- Often peritumoral edema
- Cut section is variegated (yellowish necrotic central area, grayish peripheral rim, recent and old hemorrhage, cysts due to liquefied necrotic tumor tissue)
- Usually intraparenchymal
- Infrequently superficial, may grossly / radiologically resemble metastatic carcinoma or meningioma
Gross images
Images hosted on other servers:
Variegated tumor
Microscopic (histologic) description
- High grade astrocytoma (anaplastic, nuclear atypia, cellular pleomorphism, mitotic activity) with either coagulation necrosis or microvascular proliferation (formerly "endothelial proliferation") with thickened vascular walls due to endothelial cell hyperplasia (increase in nuclei in vessel wall) and hypertrophy; also formation of multiple lumina resembling glomerulus
- Usually hypercellular with mitotic figures (some atypical), multinucleated tumor cells, bizarre nuclei, karyorrhectic cells
- May have pseudopalisading necrosis (tumor cells around necrotic zones), secondary structures of Scherer
- Other less common features: epithelial structures (glandular or ribbon-like), epithelioid cells with well delineated cytoplasmic membranes, granular cells, lipidized cells, macrophages (Arch Pathol Lab Med 2001;125:637)
- Three morphologic variants: giant cell glioblastoma, gliosarcoma, epitheloid glioblastoma
- Small cell morphology: densely packed small cells, resembles anaplastic oligodendroglioama on low power, may be calcification, perivascular pseudorosettes
Molecular / cytogenetics description
- Amplification of EGFR (particularly in small cell variant, Clin Neuropathol 2005;24:163), mutations of p16, p53 and PTEN; loss of heterozygosity at 10q
Differential diagnosis
- Lymphoma:angiocentric and angioinvasive patterns, no fibrillary background, CD45+
- Meningioma, malignant: EMA+, may contain entrapped GFAP+ glia
- Metastatic carcinoma: discrete, no fibrillary background, GFAP-, CAM5.2+ (Arch Pathol Lab Med 1999;123:917)
- Other high grade gliomas
