Approach Considerations
Classification of astrocytomas is based on distinct histopathologic and molecular alterations, and drives prognostic relevance and treatment decision making. Therefore, while clinical picture and imaging are important, tissue diagnosis is often necessary (via biopsy or surgical resection) prior to further treatment planning. The most recent World Health Organization (WHO) Classification of gliomas from 2021 is shown in the flow chart below.
Laboratory Studies
No laboratory studies are diagnostic of astrocytoma. Baseline laboratory studies that may be obtained for general metabolic surveillance and preoperative assessment include the following:
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Basic metabolic profile
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Complete blood cell count (CBC)
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Prothrombin time (PT)
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Activated partial thromboplastin time (aPTT)
Imaging Studies
Computed tomography (CT) and magnetic resonance imaging (MRI), with and without contrast, are helpful in the diagnosis and clinical decision making for patients with astrocytomas. MRI is considered the criterion standard, but a CT scan may be useful in the acute setting or when MRI is contraindicated.
On a CT scan, low-grade astrocytomas appear as poorly defined, homogeneous, low-density masses without contrast enhancement (see the image below). However, slight enhancement, calcification, and cystic changes may be evident.
Axial CT scan, precontrast and postcontrast, shows a low-grade astrocytoma of the left frontal lobe. The tumor is nonenhancing.
In cases where a cortically based enhancing mass is discovered, particularly in cases where multiple lesions are identified, the possibility of metastatic disease must be considered. Systemic imaging, generally consisting of a contrast-enhanced CT scan of the chest, abdomen, and pelvis, may be warranted to evaluate for the possibility of an alternative primary lesion.
Like low-grade astrocytomas, higher-grade astrocytomas may appear as low-density lesions or non-homogeneous lesions, with areas of both high and low density within the same lesion. Unlike low-grade lesions, partial contrast enhancement is common. [25, 26]
Astrocytomas are generally isointense on T1-weighted images and hyperintense on T2-weighted images. (See the images below.) While lower-grade astrocytomas uncommonly enhance on MRI, most higher-grade astrocytomas enhance with paramagnetic contrast agents. New methods are being developed to assess tumor vascularity by MRI, including techniques such as arterial-spin labeling (ASL) and dynamic contrast-enhanced MRI.
Coronal postcontrast T1-weighted MRI shows a low-grade astrocytoma in the right inferior frontal lobe just above the sylvian fissure. No enhancement is present post–gadolinium administration.
Axial T2-weighted MRI shows a low-grade astrocytoma of the inferior frontal lobe with mild mass effect and no surrounding edema.
Angiography may be used to rule out vascular malformations and to evaluate tumor blood supply. A normal angiographic pattern or a pattern consistent with an avascular mass that displaces normal vessels is usually observed with both low-grade and high-grade lesions. In rare instances, a tumor blush may be observed with high-grade lesions.
Imaging has also taken on a larger role in the operating room, as many procedures are now performed with intraoperative image guidance based on high-resolution MRIs. In addition, intraoperative MRI and CT scans are being tested for utility in guiding the extent of resection and presence of residual tumor during the surgical procedure.
Furthermore, other higher-dimensional preoperative imaging studies can be used to map functional areas such as those that control speech, language, and motor and sensory functions, if the tumor abuts these regions, to ensure the safe resection of the lesion while avoiding eloquent brain structures. These include functional MRI (fMRI) and diffusion tensor imaging (DTI) tractography. [27]
For more information, see Astrocytoma Brain Imaging and Spinal Imaging in Astrocytoma.
Other Tests
The following studies may be indicated in patients with astrocytoma:
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Electroencephalography (EEG) may be employed to evaluate and monitor epileptiform activity in patients with seizures associated with astrocytoma.
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Radionuclide scans, such as positron emission tomography (PET), single-photon emission tomography (SPECT), and technetium-based imaging, can permit study of tumor metabolism and brain function; PET and SPECT may be used to distinguish a solid tumor from edema, to differentiate tumor recurrence from radiation necrosis, and to localize structures.
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An electrocardiogram (ECG) and chest radiograph are indicated to evaluate operative risk.
Procedures
In addition to its therapeutic role (tumor removal or debulking), surgery in the patient with astrocytoma provides tissue for histologic/molecular diagnosis and grading, which permits tailoring of adjuvant therapy and assessment of prognosis. [28] Stereotactic biopsy is a safe and simple method for establishing a tissue diagnosis, but can be limited by quantity of tissue obtained. See Treatment/Surgical Care.
Although cerebrospinal fluid analysis is not part of the diagnosis of astrocytoma, it may help in ruling out other possible diagnoses, such as metastasis, lymphoma, or medulloblastoma. However, lumbar puncture (LP) should be approached with extreme caution in patients with cerebral astrocytomas, because of the risk of downward cerebral herniation secondary to elevated intracranial pressure.
Histologic Findings
Traditionally, astrocytomas were diagnosed and graded via histologic findings alone. Astrocytomas are generally characterized as CNS neoplasms with markers of astrocytes, including glial fibrillary acidic protein (GFAP), along with some or all of the classic histologic features of neoplastic disease, including nuclear atypia, increased mitoses, microvascular proliferation, and/or necrosis. [29] See the images below.
Higher-grade IDH-mutant astrocytoma, with nuclear atypia and mitoses. Courtesy of Wikipedia (https://en.wikipedia.org/wiki/Anaplastic_astrocytoma).
Traditionally, four histologic variants of low-grade diffuse astrocytomas had been recognized: protoplasmic, gemistocytic, fibrillary, and mixed. However, those classifications have been de-emphasized as part of the updated World Health Organization (WHO) 2021 classification, which integrates histopathologic and molecular findings for a unified diagnosis (see flow chart below). [2, 30]
The WHO grade of the tumor is of primary importance when determining prognosis and treatment (see Overview/Prognosis and Guidelines/Guidelines Summary).
Broadly, two classes of astrocytic tumors are recognized: those with narrow zones of infiltration and well circumscribed (eg, pilocytic astrocytoma, subependymal giant cell astrocytoma, pleomorphic xanthoastrocytoma) and those with diffuse zones of infiltration (eg, low-grade astrocytoma, anaplastic astrocytoma, glioblastoma).
The updated WHO criteria also make a distinction between adult-type and pediatric-type diffuse gliomas. In the updated criteria, isocitrate dehydrogenase (IDH) gene mutational status is the primary molecular alteration used for stratification of adult-type diffuse gliomas, as mutations in either gene (IDH1 or IDH2) alter disease progression, carry prognostic relevance (the IDH1/2 mutation is associated with improved survival), and guide treatment decisions. The emphasis on this molecular marker, as demonstrated in the above flow chart, has led to two major changes in the classifications of astrocytoma:
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Elimination of the entitity of IDH-mutant glioblastoma (now called WHO Grade 4 IDH-mutant astrocytoma)
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Classification of any low-grade IDH-wildtype astrocytomas as primarily pediatric-type diffuse gliomas (IDH wild type gliomas in adults tend to have one or more aggressive features that classifies them as glioblastoma WHO Grade 4).
For a discussion of glioblastoma, IDH wildtype, see Glioblastoma.
IDH-mutant astrocytomas are now defined as a distinct disease process and pathology. Oligodendroglioma, also IDH-mutated, is distinguished from astrocytoma molecularly via existence of the chromosomal co-deletion 1p-19q and retention of the ATRX gene. For a detailed discussion of pathology of IDH-mutant oligodendroglioma, see Pathology of Oligodendrogliomas.
IDH-mutant diffuse astrocytomas are graded by WHO from 2-4 as described in the flow chart above (no grade 1 IDH-mutant diffuse astrocytomas exist), and can be summarized below:
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Grade 2: No CDKN2A/B deletion, no significant mitosis, microvascular proliferation, or necrosis
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Grade 3: No CDKN2A/B deletion, microvascular proliferation, or necrosis, but significant mitotic activity
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Grade 4: Existence of CDKN2A/B homozygous deletion, microvascular proliferation, or necrosis
For more information, see Pathology of Diffuse Astrocytomas and Pathology of Expansile Astrocytomas.
Staging
Staging is not performed or described for patients with astrocytoma. IDH-mutant astrocytomas can be described as low grade (WHO grade 2) or high grade (grades 3 and 4). [31] See Workup/Histologic Findings for a complete classification via the WHO grading criteria.
Unlike other systemic tumors, distant or extracranial metastasis of astrocytomas is exceedingly rare. Clinical decline and tumor-associated morbidity and mortality are almost always associated with local mass effects on the brain by a locally recurrent intracranial tumor.
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Low-grade diffuse astrocytoma and low cellularity with minimal nuclear atypia.
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Diffuse astrocytoma with microcyst formation.
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Gemistocytic astrocytoma tumor cells have eosinophilic cytoplasm with nuclei displaced to the periphery.
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Characteristic pilocytic astrocytoma, long bipolar tumor cells, and Rosenthal fibers.
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Anaplastic astrocytoma with high cellularity with marked nuclear atypia.
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Gross specimen of a low-grade astrocytoma.
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Axial CT scan, precontrast and postcontrast, shows a low-grade astrocytoma of the left frontal lobe. The tumor is nonenhancing.
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Coronal postcontrast T1-weighted MRI shows a low-grade astrocytoma in the right inferior frontal lobe just above the sylvian fissure. No enhancement is present post–gadolinium administration.
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Axial T2-weighted MRI shows a low-grade astrocytoma of the inferior frontal lobe with mild mass effect and no surrounding edema.
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IDH-mutant astrocytoma treatment guidelines.
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Higher-grade IDH-mutant astrocytoma, with nuclear atypia and mitoses. Courtesy of Wikipedia (https://en.wikipedia.org/wiki/Anaplastic_astrocytoma).
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2021 WHO classification of gliomas.
