Anaplastic astrocytoma

Astrocytoma, IDH-mutant, specifically grade 3
Micrograph of an anaplastic astrocytoma. H&E stain.
SpecialtyNeuro-oncology, Neurosurgery
Prognosis23.6% (5-year survival)[1]

Anaplastic astrocytoma is an outdated term for a rare WHO grade 3 type of IDH-mutated astrocytoma, which is a type of cancer of the brain. In the United States, the annual incidence rate for anaplastic astrocytoma is 0.35 per 100,000 people.[2]

Signs and symptoms

Patients most often present with focal or generalized symptoms, depending on the anatomic location of the tumour. Focal symptoms may include weakness, visual impairment, language dysfunction, and gait disturbance.[3] Generalized symptoms include personality and behavioural changes, headaches, nausea, and seizures.[3] The growth rate and mean interval between onset of symptoms and diagnosis is approximately 1.5–2 years but is highly variable,[4] being intermediate between that of low-grade astrocytomas and glioblastomas.[4] Seizures are less common among patients with anaplastic astrocytomas compared to low-grade lesions.[4]

Causes

The best-known risk factor is exposure to ionizing radiation, and CT scan radiation is an important cause.[5][6] The dose-response for the relationship between low-dose ionising radiation and anaplastic astrocytoma risk is a risk increase of 115% per 100 milligray of radiation. Most high-grade gliomas occur sporadically or without identifiable cause.[7] However, a small proportion (less than 5%) of persons with malignant astrocytoma have a definite or suspected hereditary predisposition.[8] The main hereditary predispositions are mainly neurofibromatosis type I, Li-Fraumeni syndrome, hereditary nonpolyposis colorectal cancer and tuberous sclerosis.[7] Anaplastic astrocytomas have also been associated with previous exposure to vinyl chloride and to high doses of radiation therapy to the brain.[7]

Pathology

Histology

Anaplastic astrocytoma frequently contains mixed areas of low and high grade tumour, reflecting progression from a lower-grade precursor in three quarters of cases; the remaining quarter arise de novo.[3] Histologically, anaplastic astrocytoma (actrocytoma, IDH-mutant, WHO grade 3) is characterized by:

  • Increased cellularity and nuclear atypia[3]
  • Brisk mitotic activity (key feature distinguishing grade 3 from grade 2)[3]
  • Presence of glial markers (e.g., GFAP) and absence of neuronal markers[3]
  • Absence of microvascular proliferation and necrosis (features that, along with homozygous CDKN2A/B deletion, define grade 4)[3]

The MIB-1 (Ki-67) labelling index is usually 5-10% but may overlap with both low-grade astrocytoma and glioblastoma, and can show considerable variation.[3] Histologic classification alone has poor reproducibility among pathologists and correlates imperfectly with outcome; molecular classification is now considered the stronger predictor of prognosis, with the most accurate assessment achieved by combining both approaches.[9]

Molecular features

There is no single molecular marker that defines anaplastic astrocytoma. The most important molecular alterations and their clinical significance are as follows.

IDH1/IDH2 mutations

Mutations in IDH1/IDH2 are a defining feature of the parent cancer classification, astrocytoma, IDH-mutant. IDH1 is mutated in 95% of cases. Tumours with IDH mutations are associated with significantly better outcomes than those without.[3]

MGMT promoter methylation

Methylation of the MGMT promoter region is present in approximately 50% of cases.[3] It is associated with improved progression-free survival.[3]

Absent CDKN2A/B deletion

Under the 2021 WHO guidelines, presence of a CDKN2A/B deletion indicates grade 4, even in the absence of histological necrosis or microvascular proliferation.[10]

Absent 1p/19q codeletion

By definition, the presence of 1p/19q codeletion reclassifies the tumour as oligodendroglioma, IDH-mutant and 1p/19q-codeleted, under the 2021 WHO scheme.[10]

Treatment

The standard initial treatment is to remove as much of the tumor as possible without worsening neurologic deficits. Radiation therapy has been shown to prolong survival and is a standard component of treatment. Long-term follow up confirms that radiotherapy followed by adjuvant temozolomide is effective for treating recurrent anaplastic astrocytoma.[11]

Quality of life after treatment depends heavily on the area of the brain that housed the tumor. In many cases, patients with anaplastic astrocytoma may experience various types of paralysis, speech impediments, difficulties planning and skewed sensory perception. Most cases of paralysis and speech difficulties can be rehabilitated with speech, occupational, physical, and vision therapy.[12]

Prognosis

The age-standardized 5-year relative survival rate is 23.6%.[1] Patients with this tumor are 46 times more likely to die than matched members of the general population.[1] Prognosis across age groups is different especially during the first three years post-diagnosis. When the elderly population is compared with young adults, the excess hazard ratio (a hazard ratio that is corrected for differences in mortality across age groups) decreases from 10.15 to 1.85 at 1 to 3 years, meaning that the elderly population are much more likely to die in the first year post-diagnosis when compared to young adults (aged 15 to 40), but after three years, this difference is reduced markedly.[1] Typical median survival for anaplastic astrocytoma is 2–3 years. Secondary progression to glioblastoma multiforme is common. Radiation, younger age, female sex, treatment after 2000, and surgery were associated with improved survival in AA patients.[13]

References

  1. 1 2 3 4 Smoll NR, Hamilton B (October 2014). "Incidence and relative survival of anaplastic astrocytomas". Neuro-Oncology. 16 (10): 1400–7. doi:10.1093/neuonc/nou053. PMC 4165416. PMID 24723565.
  2. ↑ Smoll, Nicolas R.; Hamilton, Brett (October 2024). "Incidence and relative survival of anaplastic astrocytomas". Neuro-Oncology. 16 (10): 1400–1407. doi:10.1093/neuonc/nou053. ISSN 1523-5866. PMC 4165416. PMID 24723565.
  3. 1 2 3 4 5 6 7 8 9 10 11 Grimm, Sean A.; Chamberlain, Marc C. (July 2016). "Anaplastic astrocytoma". CNS oncology. 5 (3): 145–157. doi:10.2217/cns-2016-0002. ISSN 2045-0915. PMC 6042632. PMID 27230974.
  4. 1 2 3 Kennedy BC, Bruce JN, Shepard RC (8 December 2020). Talavera F, Engelhard HH (eds.). "Astrocytoma". Medscape. WebMD, LLC.
  5. ↑ Smoll NR, Brady Z, Scurrah KJ, Lee C, Berrington de González A, Mathews JD (July 2023). "Computed tomography scan radiation and brain cancer incidence". Neuro Oncol. 25 (7): 1368–76. doi:10.1093/neuonc/noad012. PMC 10326490. PMID 36638155.
  6. ↑ Smoll NR, Brady Z, Scurrah K, Mathews JD (June 2016). "Exposure to ionizing radiation and brain cancer incidence: The Life Span Study cohort". Cancer Epidemiol. 42: 60–5. doi:10.1016/j.canep.2016.03.006. PMID 27038588.
  7. 1 2 3 "Anaplastic Astrocytoma". Children's Hospital Boston. Archived from the original on 6 July 2010. Retrieved 1 August 2010.
  8. ↑ Dropcho EJ (December 7, 2009) [November 11, 1996]. "Malignant astrocytomas". medlink.com.
  9. ↑ van den Bent, Martin J. (September 2010). "Interobserver variation of the histopathological diagnosis in clinical trials on glioma: a clinician's perspective". Acta Neuropathologica. 120 (3): 297–304. doi:10.1007/s00401-010-0725-7. ISSN 1432-0533. PMC 2910894. PMID 20644945.
  10. 1 2 Louis, David N.; Perry, Arie; Wesseling, Pieter; Brat, Daniel J.; Cree, Ian A.; Figarella-Branger, Dominique; Hawkins, Cynthia; Ng, H. K.; Pfister, Stefan M.; Reifenberger, Guido; Soffietti, Riccardo; von Deimling, Andreas; Ellison, David W. (2021-08-02). "The 2021 WHO Classification of Tumors of the Central Nervous System: a summary". Neuro-Oncology. 23 (8): 1231–1251. doi:10.1093/neuonc/noab106. ISSN 1523-5866. PMC 8328013. PMID 34185076.
  11. ↑ van den Bent MJ, Ghisai SA, Wick W, et al. (2026). "Concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC study 26053-22054): final and exploratory analyses of a randomised, open-label, phase 3 trial". Lancet Oncology. 27 (1): 45–56. doi:10.1016/S1470-2045(25)00614-X. PMID 41449147.
  12. ↑ Chivukula, Srinivas; Pikul, Brian K.; Black, Keith L.; Pouratian, Nader; Bookheimer, Susan Y. (2018-08-01). "Contralateral functional reorganization of the speech supplementary motor area following neurosurgical tumor resection". Brain and Language. 183: 41–46. doi:10.1016/j.bandl.2018.05.006. PMC 6499625. PMID 29783125.
  13. ↑ Nuño M, Birch K, Mukherjee D, Sarmiento JM, Black KL, Patil CG (September 2013). "Survival and prognostic factors of anaplastic gliomas". Neurosurgery. 73 (3): 458–65, quiz 465. doi:10.1227/01.neu.0000431477.02408.5e. PMID 23719055.
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