Oligoastrocytoma overview

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Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Oligoastrocytoma from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Staging

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray

CT

MRI

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Other Imaging Findings

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Overview

Oligoastrocytomas are extremely rare brain tumors that together with oligodendrogliomas account for approximately 10% of primary CNS tumors. They are a subtype of gliomas and account for 25% of all gliomas. These tumors are composed of astrocytoma and oligodendroglioma. Celli et al in 1994 gave the name of "oligoastrocytoma" to those oligodendroglial tumors where the astrocytes formed more than 20% of the tumor cells. Morphologic characteristics of oligoastrocytomas resemble those of pure oligodendrogliomas and astrocytomas. Oligoastrocytomas are primarily tumors of adulthood with peak incidence in 4th to 6th decade of life. Even though these tumors can arise anywhere within the the brain, but usually in the supratentorial region, especially frontal and temporal lobes are the most common sites. Based on WHO classification, oligoastrocytomas are devided into two classes: oligoastrocytoma corresponding to grade II and anaplastic oligoastrocytoma corresponding to grade III. Clinical manifestaions of oligoastrocytoma vary and can range from seizure and headaches to personality changes. Many risk fators seem to play a role in pathogenesis of oligoastrocytoma. The molecular changes can resemble those of oligodendrogliomas (loss of heterozygosity on 1p and 19q, in 30-70% of cases) or astrocytoma (TP53 mutation and loss of heterozygosity on 17p). Treatment is based on sugery, however the tumor is responsive to chemotherapy in most cases, when necessary.

Historical Perspective

The broad topic "oligodendroglial tumors", of which oligoastrocytoma is a part of, was first described by Bailey and Cushing in 1926. They reported that gliomas were formed by transformation of glial cells.Celli et al in 1994 gave the name of "oligoastrocytoma" to those oligodendroglial tumors where the astrocytes formed more than 20% of the tumor cells.

Classification

Oligoastrocytoma may be classified according to the WHO classification of the central nervous system tumors into two subtypes: oligoastrocytoma (OAII) and anaplastic oligoastrocytoma (OAIII). OAII can evolve to OAIII overtime.

Pathophysiology

Oligoastrocytomas are mixed tumors that arise from the proliferation of both oligodendrocytes and astrocytes. Genes associated with the pathogenesis of oligoastrocytoma and anaplastic oligoastrocytoma include IDH1, p53, EGFR, ATRX, EGFR, PTEN, MGMT, CIC, and FUBP1. 30-70% of oligoastrocytomas show loss of heterozygosity (LOH) of 1p and 19q.

Causes

Common causes of oligoastrocytoma include genetic mutations and ionizing radiation. Common genetic mutations involved in the development of oligoastrocytoma can be found here. Genes associated with the pathogenesis of oligoastrocytoma and anaplastic oligoastrocytoma include IDH1, p53, EGFR, ATRX, EGFR, PTEN, MGMT, CIC, and FUBP1.

Differentiating Oligodendroglioma from other diseases

As clinical manifestation of oligoastrocytoma differ based on the site of the tumor, many disease and intracranial space occupying lesions can be named as its differential diagnosis: Astrocytoma, anaplastic astrocytoma, oligodendroglioma, pilocytic astrocytoma, central neurocytoma, ependymoma, dysembryoplastic neuroepithelial tumor, meningioma, cerebral metastasis, multiple sclerosis, and intracranial cysts.

Epidemiology and Demographics

Oligoastrocytoma is the third most common glioma. Oligoastrocytoma accounts for 1% of all brain tumors and 5–10% of all glial neoplasms. The incidence of oligoastrocytoma is approximately 0.03 per 100,000 individuals in the United States. Oligoastrocytoma is a disease that tends to affect the young and middle-aged adult population with peak incidence in 4th to 6th decades of life. The median age of diagnosis is 42 years. Males are more commonly affected with oligoastrocytoma than females. Oligoastrocytoma usually affects individuals of the Caucasian race. The incidence rate of oligoastrocytoma is higher in developed countries than in developing countries.

Risk factors

Common risk factors in the development of oligoastrocytoma include family history of brain tumors, ionizing radiation, and allergic diseases. However other risk factors such as viral infections and immune factors seem to play a role. Of these factors, only the association of ionizing radiation has been proven.

Screening

There is insufficient evidence to recommend routine screening for oligoastrocytoma.

Natural History, Complications and Prognosis

  • If left untreated, patients with oligoastrocytoma may progress to develop seizures, focal neurological deficits, hydrocephalus, brain herniation, intracranial hemorrhage, and ultimately death.[1][2][3]
  • Oligoastrocytomas are slow growing tumors.[4]
  • These tumors can evolve in terms of WHO classification from OAII to OAIII over time.
  • Common complications associated with oligoastrocytoma include hydrocephalus, intracranial hemorrhage, coma, metastasis, venous thromboembolism, and side effects of chemotherapy and radiation.[2][5][6][1][7][3]
  • Depending on the extent and grade of the tumor at the time of diagnosis, the prognosis of oligoastrocytoma may vary. However, the prognosis is generally regarded as good.[8]
  • The prognosis of low-grade oligoastrocytoma is more favorable than that for anaplastic oligoastrocytoma because of the more indolent course and younger age at which most patients are diagnosed.[2]
  • The prognosis of oligoastrocytoma is better than that of astrocytoma and poorer than that of oligodendrogliomas.
  • The 1, 5, and 10-year survival rates of patients with oligoastrocytoma are approximately 87%, 56.97%, and 45.80%, respectively.[9]

Diagnosis

Staging

There is no established system for the staging of oligoastrocytoma.[1]

History and Symptoms

When evaluating a patient for oligoastrocytoma, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough past medical history review. Other specific areas of focus when obtaining the history include review of the history of any ionizing radiation, allergic diseases, and the family history for any brain tumors.[17][18][1] Symptoms associated with oligoastrocytoma include seizure, headache, nausea, vomiting, loss of balance, vision loss, and changes in speech, mood, and personality.[19][11][20][21][6][22][1]

Physical examination

Common physical examination findings of oligoastrocytoma include:

Laboratory Findings

Some patients with oligoastrocytoma may have elevated protein and cell count with normal glucose and lactate on CSF analysis, which is usually suggestive of hydrocephalus.[23][24]

Chest X Ray

Chest x-ray may be performed to detect metastases of anaplastic oligoastrocytoma to the lungs.[25][7]

CT

  • Head CT scan may be helpful in the diagnosis of oligoastrocytoma, however it lacks the required specificity for definitive diagnosis.
  • The findings on CT scan have unsharp edges and appear as patchy lesions.
  • Tumors may show areas of calcification in CT scan.
  • Findings on CT scan suggestive of oligoastrocytoma are intra-axial low-attenuation areas with mass effect and little to no associated edema.[26]

MRI

  • Brain MRI is helpful in the diagnosis of oligoastrocytoma.
  • On brain MRI, oligoastrocytoma is characterized by a mass which is typically hypointense on T1-weighted images and hyperintense on T2-weighted images.
  • No enhancement is observed on gadolinium enhanced T1-weighted images.[27]


MRS (magnetic resonance spectroscopy)

  • Creatinine levels may be decreased.
  • Choline-containing compumds may be incresed, however, in cases of necrosis in highly malignant tumors they may be decreased.
  • Lactate levels may be increased.
  • N-acetyl aspartate can be significantly decreased.
  • MRS can help with classification of tumors as ratios of these compunds can help with classification of these malignacies.

Ultrasound

There are no specific ultrasound findings associated with oligoastrocytoma.

Other Imaging Findings

Other imaging studies for oligoastrocytoma include PET scan (accumulation of [18F]-fluorodeoxyglucose) and bone scan (bone metastasis).[28][29][30][7]

Other Diagnostic Studies

Other diagnostic studies for oligoastrocytoma include biopsy ("star-shaped" astrocytes with ovoid nucleus and homogeneous, compact oligodendrocytes with distinct borders, round nucleus, and clear cytoplasm surrounding a dense central nucleus and perinuclear halo, giving it the characteristic “fried egg” appearance) and fluorescent in-situ hybridization (FISH) technique (deletions of chromosome 1p and 19q).[31][32]

Treatment

Medical Therapy

Surgery

Surgery is the first-line treatment option for patients with oligoastrocytoma.[21][1][33][37] CSF shunting is usually reserved for patients with hydrocephalus.[24]

Primary Prevention

There are no primary preventive measures available for oligoastrocytoma.

Secondary Prevention

Patients treated for oligoastrocytoma should follow-up for secondary prevention. Secondary prevention strategies following oligoastrocytoma include a clinical assessment of neurological function and corticosteroid usage, checking for signs of venous thromboembolism, regular laboratory tests, and routine imaging (MRI and Positron Emission Tomography) at scheduled intervals after treatment.[5]

References

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  2. 2.0 2.1 2.2 2.3 Grier, J. T. (2006). "Low-Grade Gliomas in Adults". The Oncologist. 11 (6): 681–693. doi:10.1634/theoncologist.11-6-681. ISSN 1083-7159.
  3. 3.0 3.1 Specht CS, Pinto-Lord C, Smith TW, DeGirolami U, Suran E, Marshall PC; et al. (1986). "Spontaneous hemorrhage in a mixed glioma of the cerebellum: case report". Neurosurgery. 19 (2): 278–81. PMID 3748360.
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  9. One–, Two–, Three–, Four–, Five–, and 10–year relative survival rates for selected malignant brain and central nervous system tumors, Seer 17 Registries, 1995-2006. CBTRUS 2015. http://www.cbtrus.org/2010-NPCR-SEER/CBTRUS-WEBREPORT-Final-3-2-10.pdf. Accessed on October 16, 2015
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  25. Lone, N. A.; Thameem, D.; Syed, S. J.; Kingree, R. M.; Holly, J. S.; Dhand, R.; Jadhav, A. (2010). "Pulmonary Deposits of Anaplastic Oligoastrocytoma: Can It Be Prevented or Early Detected?". Chest. 138 (4 MeetingAbstracts): 64A–64A. doi:10.1378/chest.10865. ISSN 0012-3692.
  26. Radiologic features of oligoastrocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/oligoastrocytoma. Accessed on October 18, 2015
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  31. Diagnosis of oligoastrocytoma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligoastrocytoma. Accessed on October 20, 2015
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  36. Mueller W, Hartmann C, Hoffmann A, Lanksch W, Kiwit J, Tonn J; et al. (2002). "Genetic signature of oligoastrocytomas correlates with tumor location and denotes distinct molecular subsets". Am J Pathol. 161 (1): 313–9. doi:10.1016/S0002-9440(10)64183-1. PMC 1850690. PMID 12107116.
  37. Eskandar EN, Loeffler JS, O'Neill AM, Hunter GJ, Louis DN (2004). "Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 33-2004. A 34-year-old man with a seizure and a frontal-lobe brain lesion". N Engl J Med. 351 (18): 1875–82. doi:10.1056/NEJMcpc049025. PMID 15509821.


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