Malignant astrocytomas

Edward J Dropcho MD (Dr. Dropcho of Indiana University Medical Center has no relevant financial relationships to disclose.)
Originally released November 11, 1996; last updated March 30, 2014; expires March 30, 2017
Notice: This article has expired and is therefore not available for CME credit.

This article includes discussion of malignant astrocytomas and high-grade astrocytoma. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


The term “malignant astrocytoma” includes glioblastoma and anaplastic astrocytoma. Glioblastoma is the most common glioma in adults, with approximately 10,000 new cases diagnosed yearly in the United States. Unfortunately, glioblastoma is also the most lethal primary brain tumor in adults. Anaplastic astrocytoma is less common than glioblastoma and carries a somewhat better prognosis, but it still leads almost invariably to a fatal outcome. There have been tremendous advances in the understanding of the cell biology and molecular genetics of malignant astrocytomas in the past 20 years. This new knowledge is slowly but steadily leading to new therapeutic strategies. The author reviews the biology, diagnosis, work-up, prognosis, current patient management, and future therapies for malignant astrocytoma.

Key points


• Glioblastoma is the most common and most malignant primary brain tumor in adults. Anaplastic astrocytoma is less common and, on average, occurs in younger persons than glioblastoma.


• Molecular genetic abnormalities in malignant astrocytomas are complex and heterogeneous among individuals, although most tumors show dysfunction of several key molecular pathways.


• The major prognostic factors for survival among patients with malignant astrocytoma are tumor grade, patient age, and performance status at diagnosis.


• Current standard therapy for glioblastoma is aggressive surgical resection (if safe and feasible), followed by fractionated radiation therapy and temozolomide chemotherapy.


• There are numerous clinical trials of innovative therapies for patients with malignant astrocytoma, including investigational radiation therapy, other chemotherapy agents, and molecularly targeted agents.

Historical note and terminology

The first operative excision of an astrocytoma from brain with antiseptic technique and general anesthesia was performed in 1884 by Richard Godlee (Bennett and Godlee 1884). The patient presented with "violent paroxysms of lancinating pain in the head," "attacks of uncontrollable vomiting," and twitchings in the fingers and thumb of the left hand, which occurred many times a day. "An incision an inch long was made into the gray matter" of a distended ascending frontal convolution, and Godlee removed a "hard glioma about the size of a walnut.”

The earliest histologic classification of brain tumors was developed in 1926 by Bailey and Cushing, who divided astrocytic tumors into 3 groups based on clinical behavior and histology: more differentiated tumors were subdivided into fibrillary and protoplasmic astrocytomas; intermediate tumors were termed “astroblastoma”; and the most malignant tumors were termed “spongioblastoma multiforme,” now known as glioblastoma multiforme (Bailey and Cushing 1926). In 1950, Ringertz developed a 3-tiered system dividing astrocytic tumors into astrocytoma, “intermediate type” tumors, and glioblastoma multiforme (Ringertz 1950).

Also in 1950, Kernohan and Sayre developed a 4-tiered system in which astrocytomas were graded I through IV based on dedifferentiation of cellular elements and on increasing degrees of anaplasia (Kernohan and Sayre 1950). In this system, grades III and IV both had vascular proliferation and necrosis and were considered malignant astrocytomas. The distinction between grade III and IV tumors was subjective and imprecise.

In 1988, Daumas-Duport developed another 4-tiered grading system depending on the presence or absence of 4 variables: nuclear atypia, mitosis, endothelial proliferation, and necrosis (Daumas-Duport et al 1988). Grades I through IV tumors were defined by the presence of 0, 1, 2 or 3 or more of these variables, respectively.

Currently, the most commonly used classification system is that of the World Health Organization, which specifies 4 main groups of astrocytic neoplasms: pilocytic astrocytoma (grade 1), diffuse low-grade astrocytoma (grade 2), anaplastic astrocytoma (grade 3), and glioblastoma (grade 4) (Kleihues et al 2007). Anaplastic astrocytoma and glioblastoma are considered high-grade or malignant astrocytomas.

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