Brain Tumours in Childhood

Brain Tumours in Childhood

Primary central nervous system (CNS) tumors - the second most frequent malignancy in childhood and adolescence first being leukemia

Brain Tumors- constitutes 20% of childhood malignancies

Mortality = 45%.

These patients have the highest morbidity, primarily neurologic

Now outcomes is better – advancement in neurosurgery and  chemotherapy

Surgery with complete resection, radiation therapy and/or chemotherapy are used.

Myelosuppression and stem cell rescue in selected cases

Epidemiology.

There is a higher incidence of CNS tumors in infants and young children up to 7 yr of age compared with older children and adolescents

Pathogenesis.

100 histologic categories

5 categories constitute 80% of all pediatric brain tumors

(juvenile pilocytic astrocytoma, medulloblastoma/primitive neuroectodermal tumor [PNET],

diffuse astrocytomas,

ependymoma, and

craniopharyngioma

Site

infratentorial tumor location

supratentorial location

spinal cord

multiple sites

There are age-related differences in primary location of tumor

Less than 1st year of life, supratentorial tumors

Mainly choroid plexus complex tumors and teratomas

From 1-10 yr of age, infratentorial tumors

Mainly - juvenile pilocytic astrocytoma and medulloblastoma

After 10 yr of age, once again, supratentorial tumors

Astrocytoma most common

Tumors of the optic pathway and hypothalamus region, the brainstem, and pineal-midbrain region occur with a greater incidence in children and adolescents than in adults.

Male more affected in the incidence of medulloblastoma and ependymoma.

Familial and hereditary syndromes in 5% of cases

Cranial exposure to ionizing radiation in some cases

Childhood Brain Tumors  -  Histology

Medulloblastoma/PNET                                                                                              

Juvenile pilocytic astrocytoma                                                                                      

Low-grade astrocytoma                                                                                               

High-grade astrocytoma                                                                                               

Ependymoma                                                                                      

Craniopharyngioma                                                                              

Unclassified primary tumors

Choroid plexus tumors

Germ cell tumors

oligodendroglioma

meningioma

mixed tumors

pineal parenchymal tumors                   

Familial Syndromes Associated with Pediatric Brain Tumors        

                       

Neurofibromatosis

von Hippel-Lindau

Tuberous sclerosis

Li-Fraumeni (familial breast cancer in young women, with soft-tissue sarcomas in children, brain tumors and other cancers in close relatives; -mutation in the P53 gene on chromosome 17p.)

Clinical Manifestations.

The clinical presentation of patients with brain tumors depends on

            tumor location

            tumor type

            age of the child.

Signs and symptoms are due to

            obstruction of cerebrospinal fluid (CSF) drainage paths

            increased intracranial pressure (ICP)

            focal brain dysfunction.

Subtle changes in personality, speech may precede signs and symptoms of brain tumors.

In young children symptoms are similar to those of more common illnesses, such as gastrointestinal disorders.

Infants with open cranial sutures may present with macrocephaly and signs of increased ICP (vomiting, lethargy, and irritability).

The classic triad of headache, nausea and/or vomiting, and papilledema is associated with midline or infratentorial tumors.

Disorders of equilibrium, gait, and coordination = infratentorial tumors.

Torticollis = cerebellar tonsil herniation.

Blurred vision, diplopia, and nystagmus = infratentorial tumors.

Brainstem tumors = gaze palsy, cranial nerve palsies, and upper motor neuron deficits (hemiparesis, hyperreflexia, and clonus).

Supratentorial tumors = focal disorders such as motor weaknesses, sensory changes, speech disorders, seizures, and reflex abnormalities.

Infants with supratentorial tumors = hand preference.

Optic pathway tumors present = decreased visual acuity, Marcus Gunn pupil (afferent papillary defect), nystagmus, visual field defects.

Suprasellar region tumors and third ventricular region tumors = neuroendocrine deficits such as diabetes insipidus and hypothyroidism.

The diencephalic syndrome, (Euphoric cachexia) = failure to  thrive, emaciation, increased appetite, and euphoric affect, occurs in infants with glioma invading the optic chiasm and hypothalamus

Parinaud syndrome, a classic presentation of pineal region tumors

show

(1) paresis of upward gaze

(2) dilated pupil reacting to accommodation but not to light

(3) nystagmus to convergence

(4) eyelid retraction.

Spinal cord tumors and spinal cord dissemination of brain tumors

            long nerve tract motor and/or sensory deficits

            bowel and bladder deficits,

            back or radicular pain.

Patients with meningeal metastatic disease from brain tumors or leukemia may present with signs and symptoms similar to those of patients with infratentorial tumors.

Diagnosis.

1. complete history,
2. physical examination
3. neurologic assessment
4. neuroimaging and other tests

                                I.            MRI,

                             II.            endocrine function test,

                           III.            ophthalmologic examination,

                          IV.            serum and CSF measurements of ß-human chorionic gonadotropin and a-fetoprotein,

                             V.            analysis of the CSF

MRI is the neuroimaging of choice.

endocrine function test - tumors of the midline and the pituitary/suprasellar/optic chiasmal region

ophthalmologic examination = optic path region tumors = visual acuity, and fields of vision.

The suprasellar region and pineal region = germ cell tumors are common

Serum and CSF measurements of ß-human chorionic gonadotropin and a-fetoprotein can assist in the diagnosis of germ cell tumors.

Analysis of the CSF – to show meningeal spread in medulloblastoma / PNET, ependymoma, and germ cell tumors

Lumbar puncture is contraindicated

            in hydrocephalus secondary to CSF flow obstruction

            in infratentorial tumors.

Lumbar puncture in these individuals may lead to brain herniation, resulting in neurologic compromise and death.

METASTATIC TUMORS.

Metastatic spread of other childhood malignancies to the brain is uncommon.

acute lymphoblastic leukemia  & non-Hodgkin lymphoma

            = symptoms of communicating hydrocephalus.

Chloromas, = ollections of myeloid leukemia cells

Medulloblastoma = brain tumor to metastasize extraneuronally.

Complications and Long-Term Management.

70% of patients with childhood brain tumors have long-term survival

50% survivors have chronic problems as a result of their tumor and treatment.

            motor and sensory abnormalities

            seizure disorders

            developmental delays, learning disabilities

            neuroendocrine deficiencies (hypothyroidism, growth failure, delayed or absent puberty).

secondary malignancies

Future Directions.

selective chemotherapeutic agents

use of radiation therapy.

laboratory studies of genomics (Study of the structure of the genome of tumour cells, including mapping and sequencing) in childhood malignancies.

molecular biology of tumor genesis