An increased risk of astrocytic tumors has been observed in patients who receive therapeutic radiation therapy for pituitary adenomas, craniopharyngioma, pineal parenchymal tumors, germinoma, and tinea capitis. In addition, children who receive prophylactic radiation therapy of the CNS for acute lymphoblastic leukemia have an increased risk of developing astrocytomas. Recurrent lesions often signal histologic progression to a higher grade; this malignant progression is associated with a cumulative acquisition of multiple genetic alterations.
Pilocytic astrocytoma (WHO grade I) is a grossly circumscribed, slow-growing, often cystic tumor that occurs primarily in children and young adults. Histologically, pilocytic astrocytomas are composed of varying proportions of compacted bipolar cells with Rosenthal fibers and loose-textured multipolar cells with microcysts and granular bodies. This tumor is the most common glioma in children and represents 10% of cerebral and 85% of cerebellar astrocytic tumors. Occurring throughout the neuraxis, the preferred sites include the optic nerve, optic chiasm/hypothalamus, thalamus and basal ganglia, cerebral hemispheres, cerebellum, and brain stem. Pilocytic astrocytoma is the principal CNS tumor associated with neurofibromatosis type 1 (NF1). No specific cytogenetics or molecular genetics exist with this tumor. This tumor is infrequently fatal.
(Refer to the Pilocytic Astrocytomas section of this summary for treatment information.)
Diffuse astrocytoma (WHO grade II), also known as low-grade diffuse astrocytoma, is characterized by slow growth and infiltration of neighboring brain structures. Histologically, diffuse astrocytomas are composed of well-differentiated fibrillary or gemistocytic neoplastic astrocytes. This type of tumor typically affects young adults and has a tendency for malignant progression to anaplastic astrocytoma and, ultimately, glioblastoma. Diffuse astrocytomas represent 35% of all astrocytic brain tumors. They may be located in any region of the CNS but most commonly develop in the cerebrum. Three histologic variants include: fibrillary astrocytoma, gemistocytic astrocytoma, and protoplasmic astrocytoma. These types of tumors may occur in patients with inherited TP53 germline mutations (Li-Fraumeni syndrome). TP53 (also known as p53) mutations have been reported in more than 60% of the cases. The most common chromosomal alteration seen in diffuse astrocytoma is the deletion of chromosome band 17p13.1. The mean survival time after surgical intervention is in the range of 6 to 8 years, with considerable individual variation.
(Refer to the Diffuse Astrocytomas section of this summary for treatment information.)
Anaplastic astrocytoma (WHO grade III), also known as malignant astrocytoma and high-grade astrocytoma, may arise from a diffuse astrocytoma or may arise de novo without indication of a less malignant precursor. Histologically, this tumor shows increased cellularity, distinct nuclear atypia, and marked mitotic activity when compared with a diffuse astrocytoma. Anaplastic astrocytomas possess an intrinsic tendency to progress to glioblastoma. The mean age at biopsy is approximately 41 years. This tumor primarily affects the cerebral hemispheres. It has a high frequency of TP53 mutations, which is similar to that of diffuse astrocytoma. Chromosomal abnormalities are nonspecific. Many of the genetic alterations seen in anaplastic astrocytomas involve genes that regulate cell cycle progression. The mean time to progression is 2 years. Positive predictive factors include young age, high performance status, and gross total tumor resection.