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Medulloblastomas affect just under two people per million per year, and affect children 10 times more than adults. Medulloblastoma is the second-most frequent brain tumor in children after pilocytic astrocytoma and the most common malignant brain tumor in children, comprising 14.5% of newly diagnosed cases. In adults, medulloblastoma is rare, comprising fewer than 2% of CNS malignancies.
The rate of new cases of childhood medulloblastoma is higher in males (62%) than females (38%), a feature which is not seen in adults. Medulloblastoma and other PNET`s are more prevalent in younger children than older children. About 40% of medulloblastoma patients are diagnosed before the age of five, 31% are between the ages of 5 and 9, 18.3% are between the ages of 10 and 14, and 12.7% are between the ages of 15 and 19.
The cumulative relative survival rate for all age groups and histology follow-up was 60%, 52%, and 47% at 5 years, 10 years, and 20 years, respectively. Patients diagnosed with a medulloblastoma or PNET are 50 times more likely to die than a matched member of the general population.
The most recent population-based (SEER) 5-year relative survival rates are 69% overall, but 72% in children (1–9 years) and 67% in adults (20+ years). The 20-year survival rate is 51% in children. Children and adults have different survival profiles, with adults faring worse than children only after the fourth year after diagnosis (after controlling for increased background mortality). Before the fourth year, survival probabilities are nearly identical. Longterm sequelae of standard treatment include hypothalamic-pituitary and thyroid dysfunction and intellectual impairment. The hormonal and intellectual deficits created by these therapies causes significant impairment of the survivors.
In reported cases of the tumor over the last 25 years, the number of affected females with astroblastoma is significantly higher than the number of affected males. Sughrue et al. confirmed this trend, stating that 70% of the cases with clearly stated gender were female (100 cases total). While several publications support a genetic predisposition to females, the underlying reasons are still unknown.
At this point, no literature has indicated whether environmental factors increase the likelihood of astroblastoma. Although cancer in general is caused by a variety of external factors, including carcinogens, dangerous chemicals, and viral infections, astroblastoma research has not even attempted to classify incidence in this regard. The next few decades will aid in this understanding.
Medulloepithelioma carries a dismal prognosis with a median survival of 5 months.
In the United States, the annual incidence of chordoma is approximately 1 in one million (300 new patients each year).
There are currently no known environmental risk factors for chordoma. As noted above germline duplication of brachyury has been identified as a major susceptibility mechanism in several chordoma families.
While most people with chordoma have no other family members with the disease, rare occurrences of multiple cases within families have been documented. This suggests that some people may be genetically predisposed to develop chordoma. Because genetic or hereditary risk factors for chordoma may exist, scientists at the National Cancer Institute are conducting a Familial Chordoma Study to search for genes involved in the development of this tumor.
ASPS is an extremely rare cancer. While sarcomas comprise about 1% of all newly diagnosed cancers, and 15% of all childhood cancers, ASPS comprises less than 1% of sarcomas. According to the American Cancer Society, about 9530 new cases of soft tissue sarcoma will be diagnosed in the USA in 2006. This predicts under 100 new cases of ASPS. Such low numbers of occurrence seriously impede the search for a cure by making it hard to gather any meaningful statistics about the disease. As a result, finding the best treatment option often involves making a lot of educated guesses.
Work out of Huntsman Cancer Institute (HCI) in Utah has demonstrated that ASPS might be driven in part by lactate both being used as a fuel and driving angiogenesis.
Childhood rhabdomyosarcoma has been fatal. Recovery rates have increased by 50 percent since 1975. In children five years of age or younger survival rates are up to 65 percent. In adolescents younger than 15 years old, the survival rate has increased up to 30 percent.
Based on a series of 493 neuroblastoma samples, it has been reported that overall genomic pattern, as tested by array-based karyotyping, is a predictor of outcome in neuroblastoma:
- Tumors presenting exclusively with whole chromosome copy number changes were associated with excellent survival.
- Tumors presenting with any kind of segmental chromosome copy number changes were associated with a high risk of relapse.
- Within tumors showing segmental alterations, additional independent predictors of decreased overall survival were N-myc amplification, 1p and 11q deletions, and 1q gain.
Earlier publications categorized neuroblastomas into three major subtypes based on cytogenetic profiles:
- Subtype 1: favorable neuroblastoma with near triploidy and a predominance of numerical gains and losses, mostly representing non-metastatic NB stages 1, 2 and 4S.
- Subtypes 2A and 2B: found in unfavorable widespread neuroblastoma, stages 3 and 4, with 11q loss and 17q gain without N-myc amplification (subtype 2A) or with N-myc amplification often together with 1p deletions and 17q gain (subtype 2B).
Virtual karyotyping can be performed on fresh or paraffin-embedded tumors to assess copy number at these loci. SNP array virtual karyotyping is preferred for tumor samples, including neuroblastomas, because they can detect copy neutral loss of heterozygosity (acquired uniparental disomy). Copy neutral LOH can be biologically equivalent to a deletion and has been detected at key loci in neuroblastoma. ArrayCGH, FISH, or conventional cytogenetics cannot detect copy neutral LOH.
Neuroblastoma comprises 6–10% of all childhood cancers, and 15% of cancer deaths in children. The annual mortality rate is 10 per million children in the 0- to 4-year-old age group, and 4 per million in the 4- to 9-year old age group.
The highest incidence is in the first year of life, and some cases are congenital. The age range is broad, including older children and adults, but only 10% of cases occur in people older than 5 years of age. A large European study reported less than 2% of over 4000 neuroblastoma cases were over 18 years old.
Esthesioneuroblastoma is a slow developing but malignant tumor with high reoccurrence rates because of its anatomical position. The tumor composition, location and metastatic characteristics as well as the treatment plan determine prognosis. Common clinical classification systems for esthesioneuroblastoma include the Kadish classification and the Dulguerov classfictation. Histopathological characteristics on top of Kadish classification can further determine cancer prognosis. In severe, Kadish class C tumors, Haym's grades of pathology are important for prognosis. Patients with low grade Kadish class C tumors have a 10-year survival rate of 86 percent compared to patients with high grade class C tumors who have a survival rate of 28 percent. Surgically treated patients with high grade tumors are more likely to experience leptomeningeal metastases or involvement of the cerebral spinal fluid unlike patients with low grade tumors who usually only see local recurrence. Survival rates for treated esthesioneuroblastoma are best for surgery with radiotherapy (65%), then for radiotherapy and chemotherapy (51%), just surgery (48%), surgery, radiotherapy and chemotherapy (47) and finally just radiotherapy (37%). From the literature, radiotherapy and surgery seem to boast the best outcome for patients. However, it is important to understand that to some degree, prognosis is related to tumor severity. More progressed, higher grade tumors would result in chemotherapy or radiotherapy as the only treatment. It is no surprise that the prognosis would be worse in these cases.
The majority of patients can be expected to be cured of their disease and become long-term survivors of central neurocytoma. As with any other type of tumor, there is a chance for recurrence. The chance of recurrence is approximately 20%. Some factors that predict tumor recurrence and death due to progressive states of disease are high proliferative indices, early disease recurrence, and disseminated disease with or without the spread of disease through the cerebral spinal fluid. Long-term follow up examinations are essential for the evaluation of the outcomes that each treatment brings about. It is also essential to identify possible recurrence of CN. It is recommended that a cranial MRI is performed between every 6–12 months.
Esthesioneuroblastoma accounts for 2% of all intranasal tumors with an incidence of 0.4 cases per million people. Fewer than 700 cases of esthesioneuroblastoma have been seen in the US since 1988. Fewer than 400 unique cases have been reported globally. Esthesioneuroblastoma can occur at any time, with peak occurrence reported in the second and sixth decade of life.
Medulloepithelioma most commonly affect children between 6 months and 5 years; rarely, this tumour may occur congenitally or beyond this age range. Incidence is equal in males and females.
Rhabdomyosarcoma is the most common soft-tissue sarcoma in children as well as the third most common solid tumor in children. Recent estimates place the incidence of the disease at approximately 4.5 case per 1 million children/adolescents with approximately 250 new cases in the United States each year. With the vast majority of cases of RMS occurring in children or adolescents, two-thirds of reported cases occur in youths under the age of 10. RMS also occurs slightly more often in males than in females, with a ratio of approximately 1.3–1.5:1. In addition, slightly lower prevalence of the disease has been reported in black and Asian children relative to white children. In most cases, there are no clear predisposing risk factors for the development of RMS. It tends to occur sporadically with no obvious cause. However, RMS has been correlated with familial cancer syndromes and congenital abnormalities including neurofibromatosis type 1, Beckwith-Wiedemann syndrome, Li–Fraumeni syndrome, cardio-facio-cutaneous syndrome, and Costello syndrome. It has also been associated with parental use of cocaine and marijuana.
Primitive neuroectodermal tumor (PNET) is a malignant (cancerous) neural crest tumor. It is a rare tumor, usually occurring in children and young adults under 25 years of age. The overall 5 year survival rate is about 53%.
It gets its name because the majority of the cells in the tumor are derived from neuroectoderm, but have not developed and differentiated in the way a normal neuron would, and so the cells appear "primitive".
PNET belongs to the Ewing family of tumors.
Most frequent in middle-aged and older adults (age 40 and above), liposarcomas are the second most common of all soft-tissue sarcomas following malignant fibrous histiocytomas. Annually 2.5 cases occur per million population.
The prognosis for rhabdomyosarcoma has improved greatly in recent decades, with over 70% of patients surviving for five years after diagnosis.
Giant-cell lung cancers have long been considered to be exceptionally aggressive malignancies that grow very rapidly and have a very poor prognosis.
Many small series have suggested that the prognosis of lung tumors with giant cells is worse than that of most other forms of non-small-cell lung cancer (NSCLC), including squamous cell carcinoma, and spindle cell carcinoma.
The overall five-year survival rate in GCCL varies between studies but is generally considered to be very low. The (US) Armed Forces Institute of Pathology has reported a figure of 10%, and in a study examining over 150,000 lung cancer cases, a figure of 11.8% was given. However, in the latter report the 11.8% figure was based on data that included spindle cell carcinoma, a variant which is generally considered to have a less dismal prognosis than GCCL. Therefore, the likely survival of "pure" GCCL is probably lower than the stated figure.
In the large 1995 database review by Travis and colleagues, giant-cell carcinoma has the third-worst prognosis among 18 histological forms of lung cancer. (Only small-cell carcinoma and large-cell carcinoma had shorter average survival.)
Most GCCL have already grown and invaded locally and/or regionally, and/or have already metastasized distantly, and are inoperable, at the time of diagnosis.
It is classified into two types, based on location in the body: peripheral PNET and CNS PNET.
Undifferentiated pleomorphic sarcoma is regarded as the most common soft tissue sarcoma of late adult life. It rarely occurs in children. It occurs more often in Caucasians than in those of African or Asian descent and is a male-predominant disease, afflicting two males for every female.
FHCC accounts for 1-10% of primary liver cancers. It typically has a young age at presentation (20–40 years: mean age ~27 years) when compared to conventional HCC. Unlike the more common HCC, patients most often do not have coexistent liver disease such as cirrhosis.
Endodermal sinus tumor (EST), also known as yolk sac tumor (YST), is a member of the germ cell tumor group of cancers. It is the most common testicular tumor in children under 3, and is also known as infantile embryonal carcinoma. This age group has a very good prognosis. In contrast to the pure form typical of infants, adult endodermal sinus tumors are often found in combination with other kinds of germ cell tumor, particularly teratoma and embryonal carcinoma. While pure teratoma is usually benign, endodermal sinus tumor is malignant.
There are multiple genetic lesions associated with rhabdomyosarcoma, but there has been little consistent data demonstrating an association between specific genetic abnormalities and outcome. However, alveolar and embryonal types of RMS can be distinguished cytogenetically, and identification of specific genetic lesions can allow for accurate classification of the ARMS subtype when the histopathological findings are equivocal or unclear. This is valuable for clinical practice as the alveolar type presents a higher risk to the patient and will often require more aggressive treatment than the embryonal type. Up to 90% of alveolar RMS cases present with a translocations of t(2;13)(q35,q14) or, less commonly, t(1;13)(p36,q15). Both involve the translocation of a DNA binding domain of "PAX," a member of the Paired Box family of transcription factors, to a transactivation site on "FKHR", a member of the forkhead/HNF-3 transcription factor family. The t(2;13) translocation results in a fusion of the "PAX3" gene with "FKHR", while the t(1;13) translocation involves the fusion of "PAX7" with "FKHR". "PAX3" has a demonstrated role in muscle cell development, which supports its potential role in RMS. The t(2;13) translocation can result in the "PAX3-FKHR" fusion product, which is indicative of classic cystic ARMS. Cases of ARMS presenting with this fusion protein are said to be fusion-positive and are associated with a poorer prognosis than fusion-negative ARMS. Fortunately, the fusion protein presents a potential therapeutic target, but more research is needed to clarify the role of "PAX3-FKHR" in ARMS.
Embryonal RMS usually presents with a loss of heterozygosity (LOH) in the short arm of chromosome 11 (p11,15.5). This region is associated with multiple oncogenes, and the potential loss-of-function of this region is likely associated with the loss of a tumor suppressor. However, the specific consequences of this LOH at (p11,15.5) have yet to be determined. The short arm of chromosome 11 is also the site of the insulin-like growth factor 2 gene (IGF-2), which is often over-expressed in RMS.
"p"53 loss-of-function is associated with many cancers including rhabdomyosarcoma, and approximately 50% of RMS cases have been shown to carry some form of mutation to the p53 gene. Other oncogenes often associated with rhabdomyosarcoma, albeit with less frequency, include N"-myc", N"-ras", K"-ras," p"16," and c-"Met." However, it is unclear whether the mutation of the genes is directly related to the development of RMS. One study showed a that 35% of embryonal RMS tumors contained activating mutations in either N- or K-"ras," and it is worth noting that "ras" activation has been shown to block myogenic differentiation, which could help explain its potential role in rhabdomyosarcogenesis.