tending towards large size, calcifications, necrosis (tissue death), and hemorrhage (bleeding). radiological studies alone cannot identify at/rt; a pathologist almost always has to evaluate a brain tissue sample. the increased cellularity of the tumor may make the appearance on an uncontrasted ct to have increased attenuation. solid parts of the tumor often enhance with contrast mri finding on t1 and t2 weighted images are variable. precontrast t2 weighted images may show an isosignal or slightly hypersignal. solid components of the tumor may enhance with contrast, but not always. mri studies appear to be more able to pick up metastatic foci in other intracranial locations, as well as intraspinal locations. preoperative and follow-up studies are needed to detect metastatic disease. treatment surgery surgery plays a critical role in obtaining tissue to make an accurate diagnosis. surgery alone is not curative. in addition, 30% of the at/rts are located supratentorially and a predilection exists for the cerebellopontine angle, which makes surgical resection difficult. one-third or more children will have disseminated disease at the time of diagnosis. total or near-total resections are often not possible. chemotherapy around 50% of the at/rts will transiently respond, but chemotherapy by itself is rarely curative. no standard treatment for at/rt is known. various chemotherapeutic agents have been used against at/rts, which are also used against other cns tumors including cisplatinum, carboplatinum, cyclophosphamide, vincristine, and etoposide. some chemotherapy regimens are listed below: ccg clinical trial ccg-9921 was activated in 1993 and published its results in 2005. the proposed treatments did not have different outcomes and were not an improvement on prior treatments. geyer published a review of chemotherapy on 299 infants with cns tumors that evaluated response rate, event-free survival (efs), and toxicity of two chemotherapeutic regimens for treatment of children younger than 36 months with malignant brain tumors. patients were randomly assigned to one of two regimens of induction chemotherapy (vincristine, cisplatin, cyclophosphamide, and etoposide v vincristine, carboplatin, ifosfamide, and etoposide). intensified induction chemotherapy resulted in a high response rate of malignant brain tumors in infants. survival was comparable to that of previous studies, and most patients who survived did not receive radiation therapy. sarcoma protocols. there has been at least one report in the literature of malignant rhabdoid tumors of the cns being treated as a high-grade intracranial sarcoma. these three cases were treated with surgery, chemotherapy, radiotherapy and triple intrathecal chemotherapy similar to the intergroup rhabdomyosarcoma study iii guidelines. intrathecal protocols. one of the difficulties with brain and spinal tumors is that the blood brain barrier needs to be crossed so that the drug can get to the tumor. one mechanism to deliver the drug is through a device called an ommaya reservoir. this is a device which shares some characteristics with a shunt in which a tube a surgically placed in the fluid surrounding the brain and a bulb shaped reservoir attached to the tubing is placed under the skin of the scalp. when the child is to receive intrathecal chemotherapy, the drug is administered into this bulb reservoir. at other times intrathecal chemotherapeutic agents are delivered through a lumbar puncture (spinal tap). a current pediatric brain tumor consortium protocol uses intrathecal mafosfamide, a pre-activated cyclophosphamide derivative, in addition to other modalities to try to effect this tumor. high dose chemotherapy with stem cell rescue. this therapy uses chemotherapy at doses high enough to completely suppress the bone marrow. prior to instituting this therapy, the child has a central line placed and stem cells are gathered. after therapy these cells are given back to the child to regrow the bone marrow. stem cell rescue or autologous bone marrow transplantation, was initially thought to be of benefit to a wide group of patients, but has declined over the history of chemotherapy protocols. radiation therapy the traditional practice for childhood brain tumors has been to use chemotherapy and to defer radiation therapy until a child is older than three years. this strategy is based upon observations that children under three have significant long-term complications as a result of brain irradiation. however, the long-term outcomes of at/rt are so poor that some protocols call for upfront radiation therapy, often in spite of young age. the dose and volume of radiation had not been standardized, but radiation does appear to improve survival. the use of radiation has been limited in children younger than three because of the risk of severe neurocognitive deficits. protocols using conformal, local radiation in the young child are used to try to cure this tumor. external beam (conformal) radiation uses several beams that intersect at the tumor location; the normal brain tissue receives less radiation and cognitive function is thereby less affected. proton beam radiation was only offered at massachusetts general hospital in boston and at loma linda, california, as of 2002. since 2003, three or four more proton therapy centers have opened in the united states. st. jude children's research hospital is in the process of building one at their memphis, tennessee, location. some centers have since opened in europe. (germany, switzerland, and france). chromatin remodeling agents this protocol is still in preclinical evaluation. histone deacetylase inhibitors are a new class of anticancer agents targeted directly at chromatin remodeling. these agents have been used in acute promyelocytic leukemia and have been found to affect the hdac-mediated transcriptional repression. understanding of the ini1 deficiency is insufficient to predict whether hdac inhibitors will be effective against at/rts. some laboratory results indicate it is effective against certain at/rt cell lines. prognosis the prognosis for at/rt has been very poor, although some indications exist that an irsiii-based therapy can produce long-term survival (60 to 72 months). two-year survival is less than 20%, average survival postoperatively is 11 months, and doctors often recommend palliative care, especially with younger children because of the poor outcomes. recently, a protocol used by a multicenter trial reported in the journal of clinical oncology resulted in a 70% survival rate at 2–3 years, with most relapses occurring within months, leading to hope that a point exists beyond which patients can be considered cured. patients with metastasis (disseminated tumor), larger tumors, tumors that could not be fully removed, or tumor recurrence, and who were younger than 36 months had the worst outcomes (i.e., shorter survival times). a retrospective survey from 36 at/rt cases at st. jude children's hospital from 1984 to 2003 showed that the two-year event-free survival (efs) for children under three was 11%, and the overall survival (os) rate was 17%. for children aged 3 years or older, the efs was 78% and the os 89%. a retrospective register at the cleveland children's hospital on 42 at/rt patients found median survival time is 16.25 months and a survival rate around 33%. one-quarter of these cases did not show the mutation in the ini1/hsnf5 gene. the longest-term survivals reported in the literature are: (a) hilden and associates reported a child who was still free from disease at 46 months from diagnosis. (b) olson and associates reported a child who was disease free at five years from diagnosis based on the irs iii protocol. (c) in 2003, hirth reported a patient who had been disease-free over six years. (d) zimmerman in 2005 reported 50-to-72 month survival rates on four patients using an irs iii-based protocol. two of these long-term survivors had been treated after an at/rt recurrence. (e) a nyu study (gardner 2004) has four of 12 longer-term at/rt survivors; the oldest was alive at 46 months after diagnosis. (f) medical university of vienna, 2013, reported a 16-year survivor, among other long-term survivors cancer treatments in long-term survivors who are children usually cause a series of negative effects on physical well-being, fertility, cognition, and learning. metastasis metastatic spread is noted in roughly one-third of the at/rt cases at the time of diagnosis, and tumors can occur anywhere throughout the cns. the asco study of the 188 documented at/rt cases prior to 2004 found 30% of the cases had metastasis at diagnosis. metastatic spread to the meninges (leptomenigeal spread sometimes referred to as sugar coating) is common both initially and with relapse. average survival times decline with the presence of metastasis. primary cns tumors generally metastasize only within the cns. one case of metastatic disease to the abdomen via ventriculoperitoneal shunt has been reported with at/rt . metastatic dissemination via this mechanism has been reported with other brain tumors, including germinomas, medulloblastomas, astrocytomas, glioblastomas, ependymomas, and endodermal sinus tumors. guler and sugita separately reported cases of lung metastasis without a shunt. epidemiology an estimated 3% of pediatric brain tumors are at/rts, although this percentage may increase with better differentiation between pnet/medulloblastoma tumors and at/rts. as with other cns tumors, more males are affected than females (ratio 1.6:1). the asco study showed a 1.4:1 male to female ratio. history atypical teratoid/rhabdoid tumor was first described as a distinct entity in 1987. before 1978, when rhabdoid tumor was described, at/rt likely was misdiagnosed as medulloblastoma. in some early reports the tumor was known also as malignant rhabdoid tumor (mrt) of the cns. between 1978 and 1987, at/rt was usually misdiagnosed as rhabdoid tumor. however, both at/rt and non-cns mrt have a worse prognosis than medulloblastoma and are resistant to the standard treatment protocols for medulloblastoma. by 1995, at/rt had become regarded as a newly defined aggressive, biologically unique class of primarily brain and spinal tumors, usually affecting infants and young children. in january 2001, the u.s. national cancer institute and office of rare diseases hosted a workshop on childhood atypical teratoid/rhabdoid tumors of the central nervous system. twenty-two participants from 14 institutions came together to discuss the biology, treatments, and new strategies for these tumors. the consensus paper on the biology of the tumor was published in clinical research. the workshop's recognition that cns atypical teratoid/rhabdoid tumors (at/rt) have deletions of the ini1 gene indicates that rhabdoid tumors of the kidney and brain are identical or closely related entities. this observation is not surprising because rhabdoid tumors at both locations possess similar histologic, clinical, and demographic features. research directions atypical teratoid rhabdoid tumor is rare, and no therapy has been proven to deliver long-term survival, nor a set of protocols made standard. thus, most children with at/rt are enrolled in clinical trials to attempt to find an effective cure. a clinical trial is not a treatment standard; it is research. some clinical trials compare an experimental treatment to a standard treatment, but only if such a standard treatment exists. research into stem cell transplant surgeries is ongoing. society and culture in 2011, the new yorker published an article by aleksandar hemon, about the author's daughter's battle with at/rt. in august 2011, a 6-year-old named avalanna routh who was battling at/rt at dana–farber cancer institute was given a pretend wedding with her idol justin bieber, with doctors and nurses providing a cardboard life-sized cutout of bieber, a guitarist, flowers, and a t-shirt emblazoned with the words "future mrs. bieber". in february 2012, she spent the day in person with justin bieber, her pretend husband, after a facebook campaign to meet her idol. on september 26, 2012, she died after battling at/rt for five and a half years. the video game that dragon, cancer is based on the experiences of ryan and amy green raising their son joel after he was diagnosed with an atypical teratoid rhabdoid tumor at 12 months and given only about four months to live. joel continued to survive for four more years after developing seven additional tumors and eventually dying from cancer on march 13, 2014. ryan green wanted to provide the experiences of raising joel in the form of a video game to help the player to understand the difficulties and realities with which they had to deal during this time. after joel's death, the game was reworked to instead act as a tribute to ryan and amy's five short years with their third child. the green family's experiences are also documented in the film thank you for playing.