Diffuse Gliomas: A strocytic

Peak incidence in fourth decade, with wide age range

Slight male predominance (1.18 to 1)

Accounts for 10% to 15% of all astrocytic tumors and about 5% of all primary intracranial tumors

Typically found within the cerebral hemispheres, with propensity for frontal and temporal lobes, but can be found anywhere in the central nervous system

Seizure is common presenting symptom

Other symptoms include speech difficulty, behavior changes, or motor deficits

Treatment includes surgical resection and radiotherapy

Average mean survival is 6 to 8 years with individual variation

Typically progress toward a higher-grade astrocytic glioma

Better prognosis with younger age, complete resection, and seizure at presentation

Worse prognosis with older age, large tumor size, and neurologic deficit at presentation

MRI typically reveals an ill-defined, homogenous mass

Hypodensity on T1-weighted images without contrast enhancement

Appear bright on T2-weighted or fluid attenuation recovery (FLAIR) sequences

Ill-defined lesions with blurring of the gray-white matter junction

May be gray or yellow-white without tissue destruction

Can be cystic

Well-differentiated astrocyte-like cells—usually without distinct cell borders

Variably increased cellularity with irregular distribution of tumor cells

Nuclear pleomorphism—some cells with enlarged, hyperchromatic nuclei

May be microcystic

Mitotic activity absent or very rare; no necrosis or microvascular proliferation

Fibrillary astrocytoma

• Prototypical and most common variant

• Consists of neoplastic astrocytes in dense fibrillary background

• Cells often have inconspicuous cytoplasm: “naked” nuclei

• Nuclei can be atypical, with elongation and irregular nuclear contours

• Often has extensive microcyst formation

Gemistocytic astrocytoma

• Tumor composed of plump, angular cells with eosinophilic, glassy cytoplasm and short, haphazardly arranged processes

• Consists of at least 20% neoplastic gemistocytes

• Nuclei are eccentrically located and tend to be round and hyperchromatic

• Perivascular lymphocytic infiltrates are common findings

• Tend to have higher rate of malignant transformation compared to other diffuse astrocytomas

Protoplasmic astrocytoma

• Rare variant—controversial

GFAP can be seen in all diffuse astrocytomas with a near 100% sensitivity, but it is also positive in reactive astrocytes

TP53 reactivity in more than half of tumors

S-100 is positive, but not specific

Ki-67 mitotic labeling index is typically less than 4%

P53 mutation seen in 60% of tumors (near 90% in gemistocytic astrocytoma)

Isocitrate dehydrogenase-1 ( IDH-1 ) mutations in a subset of cases; the mutated form of this protein can be detected by immunohistochemistry in low-grade and intermediate-grade gliomas of the astrocytoma and oligodendroglioma groups

Reactive gliosis—will typically have evenly spaced astrocytes with eosinophilic cytoplasm and radially oriented cell processes

Oligodendroglioma—defined by cytologic uniformity; tumor cells with small, round regular nuclei with clear perinuclear halos; tend to be p53 negative