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Astroblastoma

Astroblastoma is a rare, glial tumor derived from the astroblast, a type of cell that closely resembles spongioblasts and astrocytes. Astroblastoma cells are most likely found in the supratentorial region of the brain that houses the cerebrum, an area responsible for all voluntary movements in the body. It also occurs significantly in the frontal, parietal, and temporal regions, areas where movement, language creation, memory perception, and environmental surroundings are expressed. These tumors also occur in major brain areas not associated with the main cerebral hemispheres, including the cerebellum, optic nerve, cauda equina, hypothalamus, and brain stem.

The most defining symptom of astroblastoma, regardless of location, is elevated intracranial pressure, which occurs when cerebrospinal fluid in the brain exhibits heavy pressure and decreased blood flow, resulting in throbbing headache or nausea for the patient. Astroblastoma is rarely observed in the oncology sphere, accounting for only 0.45% - 2.8% of all brain gliomas since its discovery in 1926.

=Classification= The World Health Organization, a specialized agency that classifies abnormal tumors affecting the central system and their risk to life, has difficulty in assigning a grade for astroblastoma. The organization’s most recent grade in 2007 assigned astroblastoma as a high grade III and grade IV neoplasm, which signifies that the glial tumor is dangerous for patients and may cause problems even after surgery. However, data compilation from a recent 2011, one that compiled nearly 30 years of astroblastoma clinical information, confirms opposite results from patients; a 95% survival rate exists after the tumor is completely removed (gross total resection). Therefore, the most important factor for any patient when cancer is concerned – the likelihood of surviving – is still controversial for astroblastoma.

=Subtypes=

Astroblastoma can be divided into low-grade, well-differentiated high-grade, and anaplastic subtypes with a spherical solid or cystic structure comprising a peripheral vasculature and epithelioid neoplasms.

General Pathology
Astroblastoma through a stable set of well-established qualities over the last decade:


 * Appear "bubbly" in nature
 * Polarized, unipolar in structure
 * Single peripheral vasculature
 * Radial arrangement as a pseudorosette
 * Immunoreactive for GFAP and vimentin (astrocytic origin)
 * Lack "true rosette" architecture
 * Lack of cohesiveness
 * Pseudopapillae formation
 * Localization mostly in cerebral hemispheres
 * Nodular, non-invasive growth
 * Strong vasculature
 * Vascular fibrosis occurrence
 * High likelihood of hyalinization
 * Generally do not metastasize toward other regions of the brain

Abnormal Pathology
The presence of bulky calcification with punctate (pointed) and globular characteristics was noted in a 2009 study of a 12 year-old girl Computerized tomography confirmed these calcified masses in the posteroinferior region to the fourth ventricle just above the midline. The mass began at the brainstem, extended along the inferior cerebellar peduncle to roof areas against the ventricles through the nodule of vermis, easily being detected against normal grey matter surrounding it. Calcification deriving from nervous system tumors is a rare quality in astroblastoma patients. Lumbar pain and lower body weakness is also a rarity in astroblastoma patients, although it it is entirely possible for astroblastoma to spread beyond the brain toward the spinal cord.

Associations with Other Tumors
An enormous difficulty lies in classifying an astroblastoma tumor since other tumors are so closely related. Certain neuroradiologic features distinguish astroblastoma from the moreso common ependymoma, a tumor occurring in the fourth ventricle within the central nervous system. When lesions are small, distinguishing between these features is difficult, and often confuse astroblastoma with glial neoplasm, high-grade astrocytic tumors, and embryonal neoplasms. Ependymoma occur in the infratentorial region adjacent to ventricles, and the “bubbly” appearance in astroblastoma is not observed in these to tumors.

With this in mind, researchers have concluded that astroblastoma is considered a distinct entity in comparison to olidendrogliomas (invasive, nodular cysts that may appear bubbly), pleomorphic xanthoastrocytoma, dysembryoplastic neuroepithelial tumor, juvenile pilocytic astrocytomas, and hemangioblastomas (mural nodules with a single cyst). Advances in the 21st century of histology have confirmed the uniqueness and validity of astroblastoma in the medical community compared to the past.

Research going back to early 2000 marks the complications in satisfying requirements radiographic and histopathologic findings in astroblastoma. Seven cases of comparative genomic hybridization, a molecular technique analyzing chromosomal changes in DNA content of brain cancer cells, indicated that chromosome 19 and chromosome 20q were amplified in astroblastoma cells throughout the brain. These genomic features are responsible for widespread proliferation, tumorigenesis, and deregulation of pathways associated with normal housekeeping. Furthermore, the absence of chromosome function in 9q, 10, and X were not observed in other types of neoplasms, such as an ependymoma, lending to an effective characterization of astroblastoma. Furthermore, specific neuronal markers further help to distinguish astroblastoma. Neuron-specific enolase (NSE) positive, NSE negative,synaptophysin negative, neurofilament negative, TUJ1 positive, and nestin positive have been expressed in astroblastoma cell population.

=Symptoms=

The most common symptoms of astroblastoma include:


 * Intracranial pressure
 * Enhanced drowsiness when waking up
 * Impaired vision
 * Motor system imbalance and weakness
 * Frequent nausea due to dizziness
 * Lethargic movement in the daytime
 * Psychotic episodes
 * Personality changes
 * Decreased sensation
 * Seizures with varying degrees

Case reports indicate that mild headaches, drowsiness, and weakness in motor systems when lesions impact certain areas of the brain, especially in the frontoparietal lobe. Magnetic resonance imaging can evaluate degree of swelling to the patient, and normally a physician will evaluate an astroblastoma as simply a "brain mass" in order to refer the case towards a certified oncologist. Some patients do not notice any immediate signs until the astroblastoma develops to the point where frequent falls and injuries occur. In more cases, horizontal nystagmus and other involuntary eye disorders can accompany a patient's hallucinated state of mind if the tumor is undiagnosed. Although the symptoms are wide-ranging and variable among the patient, focal deficits and nausea are extremely common regardless of gender. In rare cases, an altered mental status (such as psychotic changes and personality disorders listed above) will occur, but they are seldom found in astroblastoma patients, suggesting that additional medical problems may exasperate the nervous system.

=Epidemiology=

Astroblastoma mainly affects children, teenagers, and prominent peaks in young adulthood. Thus, astroblastoma can be considered a pediatric disease, one that continues to affect individuals through adulthood, but does not necessarily affect their survival rate.

Age Incidence
A prominent peak for incidence lies from ages 5-10 and does not become more prominent until ages 20-30 and 31-40. Currently the most common age range for diagnosis is between 10-30 years of age. A combination of anatomic location and image assessment can be coupled with the age to efficiently evaluate astroblastoma.

Gender Incidence
In many reported cases of the tumor over the last 25 years, the number of affected girls with astroblastoma has been much larger than the number of affected boys, indicating a gender predisposition toward females.

=Recurrence=

As it stands, an unfavorable prognosis exists for patients with high-grade, anaplastic astroblastoma and a favorable prognosis exists for patients with well-differentiated, low-grade astroblastoma.

Low-grade
The likelihood of a low-grade astroblastoma returning after surgery is highly improbable, but some patients do exhibit a recurrence. Therefore, the strict black-and-white diagnosis of an astroblastoma based on its grade does not determine all tumor behaviors. Patients with low-grade lesions can remain asymptomatic after surgery and show recurrence 1-2 years in follow-up sessions. Since tumor size is a large determinant for profiling severity, it is almost never the case that a low-grade astroblastoma continues to appear in size and strength after the second resection.

High-grade
Surviving high-grade astroblastoma is not outright life-threatening, but a significant portion of patients do not survive its effect due to recurrence. Unlike conventional low-grade tumors, high-grade tumors associate a number of other factors when they travel to other areas of the body, creating complications in surgery since the tumor is so prominent."Unal"/> Cases in literature confirm that high-grade patients will face up to five or six resection surgeries and still experience symptoms post-operatively. The dual-action of chemotherapy and radiotherapy can prevent recurrence when gross total resection is performed multiple times.

=Treatment=

The most common treatments for astroblastoma remain the following:


 * Gross-total resection
 * Sub-total resection
 * Radiotherapy
 * Chemotherapy

Gross-total resection
Complete surgical resection remains the standard for treating astroblastoma, despite the high recurrence rate for high-grade tumors. Since there are so few cases reported around the world each year, the standard for surgery varies from physician to physician and is often difficult to rightfully diagnose. Low-grade astroblastomas exhibit low recurrence rates following resection, but varying reports prove that some patients, despite the severity of the lesion, will unpredictably find recurrence. In a recent study of a 17-year-old male, a low-grade astroblastoma was resected and recurred within 5 months of the therapy, forcing the oncologist to administer further chemotherapy, radiotherapy, and a second resection to completely put the tumor in remission.

Radiotherapy
The use of radiation therapy after an astroblastoma excision has variable results. Conventional external beam radiation has both positive and negative effects on patients, but it is not recommended at this point to treat all types. All in all, the radiosensitivity of astroblastoma to therapy remains unclear, since some research advocate its effectiveness while others diminish the effects. Future studies must be done on patients with both total excision and sub-excision of the tumor to accurately assess whether radiation benefits patients under different circumstances.

Chemotherapy
Normally, chemotherapy is not recommended until the second required resection, which implies that the astroblastoma is a high-grade tumor continuing to recur every few months. A standard chemotherapy protocol starts with two rounds of nimustine hydrochoride (ACNU), etoposide, vincristine, and interferon-beta.. The patient undergoes am strict drug regimen until another surgery is required. By the third surgery, should recurrence in the astroblastoma occur, a six-round program ifosfamide,cisplatin, and etoposide will "shock" the patient's system to the point where recurrence is halted. Unfortunately, chemotherapy may not always be successful with patients requiring further resection of the tumor, since the tumor cell begins to show superior vasculature and a strong likelihood of compromising a patient's well-being. Oral ingestion of temozolomide for at-home bedside use may be preferred by the patient.

Forward-Looking Advances
A popular and new-age form of surgery involves CyperKnife radiotherapy and Gamma Knife radiosurgery. Their success-rate on cranial lesion is fairly effective, but recurrence is still a problem for severe patients.

One of the more exciting and promising routes for treatment involves stem cell use to combat astroblastoma. A study in 2005 profiled cell surface markers of astroblastoma cells removed from a 11 year-old patient. Fluorescence activation suggested that about 1/4 of these cells from were CD133 positive and CD24, CD34, and CD45 negative, a specific genetic makeup that lends to self-renewal, differentiation, and propagation of neural stem cells in the brain. However, the work remains a preliminary insight into the role of neuronal stemlike cells on astroblastoma development.