Pineoblastoma
Definition
A pineoblastoma is an aggressive primary brain tumor that develops in the pineal body (sometimes called the epiphysis cerebri or pineal gland), which is a small cone-shaped organ located in the midbrain. The pineal body secretes melatonin, a hormone that regulates moods and the sleep-wake cycle in humans. Pineoblastomas are also known as pinealoblastomas.
Description
Pineoblastomas are rapidly growing tumors, and thereby distinguished from pineocytomas, which grow relatively slowly. They are defined by the World Health Organization (WHO) as primitive neuroectodermal tumors (PNETs) in the pineal gland; the word primitive in this context means that these tumors are composed of cells that have not yet separated into more specialized types of cells. The word neuroectodermal means that these tumors develop out of a layer of cells in the embryo that eventually gives rise to the baby's nervous system.
Pineoblastomas are considered highly malignant. They may invade nearby areas of brain tissue as well as spread into the cerebrospinal fluid, although they rarely metastasize to other parts of the body. In addition, pineoblastomas sometimes cause bleeding into the ventricles of the brain. The child's radiologist may be able to see areas of dying tissue in the brain when imaging studies are performed.
Demographics
Pineoblastomas are extremely rare, accounting for only 0.5–2 percent of childhood tumors of the central nervous system (CNS). About 2200 children below the age of 15 are diagnosed with malignant tumors of the brain and spinal cord each year in the United States; between 10 and 40 of these children will be diagnosed with pineoblastomas.
It is difficult to evaluate the statistical significance of racial or gender differences in such a small group; however, the available evidence from American cancer registries suggests that these cancers occur more frequently in Caucasian children than in African Americans, and more frequently in males than in females.
Pineoblastomas occur almost exclusively in younger children, with very few cases reported in adolescents or adults. The slower-growing pineocytomas, by contrast, are most likely to develop in adults between the ages of 25 and 35.
Causes and Symptoms
The cause of pineoblastomas is unknown, as of early 2005, but may be associated with gene mutations. A group of British radiologists reported in 2004 that the chances of survival in children diagnosed with pineoblastoma who had inherited a mutation of the retinoblastoma (RB) gene are much lower than the chances of children who did not inherit the RB mutation. The researchers suggested that this mutation may cause pineoblastomas as well as reduce or inhibit their response to therapy.
The symptoms of a pineoblastoma result from blockage of the flow of cerebrospinal fluid and increased pressure on the brain. Depending on the size of the tumor, symptoms may include the following:
headache
double vision
nausea and vomiting
weakness or loss of sensation on one side of the body
seizures
developmental delays or failure to thrive (in younger children)
lowered energy level or unusual need for sleep
personality changes
unexplained changes in weight or appetite
Diagnosis
The diagnosis of a pineoblastoma begins with a review of the child's medical history and a thorough physical examination. The child may be given several vision tests if he or she is seeing double or having other visual disturbances. The child's doctor will then order both laboratory tests and imaging studies. The laboratory tests are done to rule out such diseases as meningitis and to see whether the child's liver and other organs are functioning normally. The imaging studies are performed to determine the extent of the cancer and to assign the child to a risk group.
Unless surgical removal of the tumor is considered too risky, a neurosurgeon will perform what is known as an open biopsy to confirm the diagnosis of pineoblastoma. He or she will remove a small piece of the tumor for examination by a pathologist.
Laboratory Tests
Standard laboratory tests for children with brain tumors include a complete blood count (CBC), electrolyte analysis, tests of kidney, liver, and thyroid function, and tests that determine whether the child has been recently exposed to certain viruses. In addition, a lumbar puncture will be performed to look for cancer cells in the child's spinal fluid.
Imaging Tests
Imaging tests for pineoblastomas include the following:
Magnetic resonance imaging (MRIs).
Computed tomography (CT) scan. Doctors usually order MRIs and CT scans that cover the full length of the spinal column as well as the brain, because pineoblastomas are more likely than other PNETs to spread into the cerebrospinal fluid.
Chest x ray.
Bone scan. This test is necessary to determine whether the tumor has spread beyond the central nervous system.
Treatment Team
Since the 1960s, most children diagnosed with brain tumors have been treated in specialized children's cancer centers. A child with pineoblastoma will usually have a pediatric oncologist as his or her primary doctor, along with one or more specialists. These specialists may include a neurosurgeon, pathologist, neuroradiologist, radiation oncologist, medical oncologist, endocrinologist, nutritionist, physical therapit or rehabilitation specialist, and psychologist or psychiatrist. The team will also include social workers, clergy, and other professionals to help the parents cope with the stresses of their child's illness and treatments.
Clinical Staging, Treatments, and Prognosis
Staging
Pineoblastomas are not staged in the same way as cancers elsewhere in the body. Instead, children with these tumors are divided as of the early 2000s into two risk groups, average risk and poor risk. Assignment to these groups is based on the following factors:
child's age
size and location of the tumor
whether the tumor has spread to other parts of the central nervous system
whether the tumor has spread beyond the CNS to other parts of the body
Average-risk children are those older than three years, with most or all of the tumor removed by surgery and no evidence that the cancer has spread beyond the pineal body. Poor-risk children are those who are younger than three years, whose cancer was located near the center of the brain or could not be removed completely by surgery, and whose cancer has spread to or beyond other parts of the CNS. The risk of recurrence is higher for children in the poor risk group.
Treatments
Treatments for pineoblastoma depend on the child's age and his or her risk group. Children younger than three years are not usually given radiation therapy because it can affect growth and normal brain development; they are usually treated with surgery to remove as much of the tumor as possible, followed by chemotherapy if they are considered poor-risk patients. The drugs most commonly used to treat PNETs include lomustine, cisplatin, carboplatin, and vincristine.
In addition to removing the tumor, the surgeon may also place a shunt to reduce pressure on the child's brain if the tumor is blocking the flow of cerebrospinal fluid. The shunt is a plastic tube with one end placed within the third ventricle of the brain. The rest of the shunt is routed under the skin of the head, neck, and chest with the other end placed in the abdomen or near the heart. Shunts are used very conservatively in children with pineoblastomas, however, because there have been reports of these tumors spreading into the abdomen via the shunt.
Children three years and older are treated with surgery first, followed by radiation treatment of the entire brain and spinal cord. Those considered poor risks may also be given chemotherapy. Recurrent pineoblastomas are treated with further surgery and an additional course of chemotherapy.
Treatments for pineoblastoma that are considered experimental as of 2005 include the following:
Gamma knife surgery (GKS). One group of neurosurgeons in Florida has reported good results in treating children with tumors in the pineal body with GKS. The advantages of GKS include more complete tumor removal and quicker recovery for the patient.
Gene therapy.
High-dose chemotherapy.
Photodynamic therapy.
Stem cell and bone marrow transplantation.
Newer drugs: Irinotecan, tipifarnib, lapatinib, ixabepilone, cilengitide, and tariquidar.
Prognosis
The prognosis for children with pineoblastomas depends largely on their risk group. In general, however, these tumors have a poorer prognosis than other types of brain tumors, in part because of the difficulty of removing the complete tumor due to the location of the pineal body deep within the brain. The overall five-year survival rate of children with pineoblastoma is reported to be 50–60 percent, but is much lower in children younger than three years and in older children who do not respond to radiation therapy.
Recurrent pineoblastomas are almost always fatal; there are no effective therapies for recurrent PNETs, as of the early 2000s.
Alternative and Complementary Therapies
Some complementary therapies that are reported to help children with pineoblastomas include pet therapy, humor therapy, and music therapy. All of these can be pleasurable for the child as well as relaxing. Ginger or peppermint may help to relieve the nausea and vomiting associated with chemotherapy.
Coping With Cancer Treatment
Children can be given additional medications to treat nausea and other side effects of chemotherapy. With regard to homesickness and other emotional reactions to being away from home, children's cancer centers have social workers and child psychologists who can educate the child's family about the cancer as well as help the child deal with separation issues.
The side effects of radiation therapy in children with brain tumors may include the formation of dead tissue at the site of the tumor. This formation is known as radiation necrosis. It occurs in about 5 percent of children who receive radiation therapy and may require surgical removal. Radiation necrosis, however, is not as serious as recurrence of the tumor.
Children who have difficulty speaking after brain surgery, or who experience physical weakness, difficulty walking, visual impairment, or other sensory problems, are given physical therapy and/or speech therapy on either an inpatient or outpatient basis.
Clinical Trials
Because pineoblastomas are so rare, the American Cancer Society recommends that children diagnosed with these tumors be enrolled in an appropriate clinical trial. As of early 2005, there are about 30 clinical trials in the United States for children with pineoblastomas and other PNETs. Some of these trials involve gene testing to improve diagnosis of children with brain tumors, while others are exploring various combinations of chemotherapy (including new agents), photodynamic therapy, stem cell transplantation, and bone marrow transplantation as treatments for pineoblastomas.
Prevention
There is no way to prevent pineoblastomas as of the early 2000s because their cause is still unknown.
Special Concerns
Children diagnosed with pineoblastomas, like children with other long-term illnesses, may develop emotional problems in reaction to restrictions on their activities, uncomfortable treatments, or being treated in a cancer center away from home. These children may withdraw from others, become angry or bitter, or feel inappropriately guilty about their illness. It is important to reassure the child that he or she did not cause the cancer or deserve it as a punishment for being "bad." Parents may benefit from consulting a child psychiatrist about these and other emotional problems.
Another special concern is the task of explaining the child's illness and treatments to other family members and friends in ways that they can understand. Members of the child's treatment team can be helpful in providing simplified descriptions for siblings or schoolmates.
Questions to Ask Your Doctor
Which risk group has my child been assigned to?
What treatments would you recommend for a child in that group, and why would you recommend them?
Is my child eligible for any current clinical trials for children with pineoblastoma?
Would you recommend any of the treatments currently considered experimental?
What is my child's life expectancy? What can I do to make the remaining time as pain-free and enjoyable as possible?
A third area of concern with childhood cancers is the parents' relationships with their other children and with each other. Siblings may resent the amount of time and attention given to the child with cancer, or they may fear that they too will develop a brain tumor. Support groups for families of children with cancer can help by sharing strategies for coping with these problems as well as allowing members to express anxiety and other painful feelings in a safe setting.
Resources
Books
American Brain Tumor Association (ABTA). A Primer of Brain Tumors. Des Plaines, IL: ABTA, 2004. The entire book can be downloaded free of charge as one large PDF file from the ABTA website.
"Intracranial Neoplasms (Brain Tumors)." Section 14, Chapter 177 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 2004.
Pelletier, Kenneth R., MD. The Best Alternative Medicine. New York: Simon & Schuster, 2002.
Periodicals
Amendola, B. E., A. Wolf, S. R. Coy, et al. "Pineal Tumors: Analysis of Treatment Results in 20 Patients." Journal of Neurosurgery 102 (January 2005) (Supplement): 175–179.
Bruce, J. N., and A. T. Ogden. "Surgical Strategies for Treating Patients with Pineal Region Tumors." Journal of Neurooncology 69 (August-September 2004): 221–236.
MacDonald, Tobey, MD. "Medulloblastoma." eMedicine, 29 July 2004. .
Plowman, P. N., B. Pizer, and J. E. Kingston. "Pineal Parenchymal Tumours: II. On the Aggressive Behaviour of Pineoblastoma in Patients with an Inherited Mutation of the RB1 Gene." Clinical Oncology (Royal College of Radiology) 16 (June 2004): 244–247.
Young, Guy, MD, Jeffrey A. Toretsky, MD, Andrew B. Campbell, MD, and Allen E. Eskenazi, MD. "Recognition of Common Childhood Malignancies." American Family Physician 61 (April 1, 2000): 2144–2154.
Organizations
American Academy of Child and Adolescent Psychiatry. 3615 Wisconsin Avenue, NW, Washington, DC 20016-3007. (202) 966-7300. Fax: (202) 966-2891. .
American Brain Tumor Association (ABTA). 2720 River Road, Des Plaines, IL 60018. (800) 886-2282 or (847) 827-9910. . This independent nonprofit association supports research as well as providing patient and family education materials.
CureSearch Children's Oncology Group (COG) Research Operations Center. 440 East Huntington Drive, P. O. Box 60012, Arcadia, CA 91066-6012. CureSearch is a joint effort of two organizations, the Children's Oncology Group (COG) and the National Childhood Cancer Foundation (NCCF). The COG conducts research and clinical trials while the NCCF conducts fundraising and advocacy initiatives.
Other
American Academy of Child and Adolescent Psychiatry (AACAP). The Child with a Long-Term Illness. AACAP Facts for Families #19. Washington, DC: AACAP, 1999.
American Cancer Society (ACS), Cancer Reference Information. Brain and Spinal Cord Tumors in Children.. .
—Rebecca Frey, PhD