BRAIN TUMORS Jeanette Norden, Ph.D. Professor Emerita Vanderbilt University School of Medicine CNS TUMORS CNS tumors (neoplasms): abnormal masses of cells produced by uncontrolled cellular proliferation; can be Primary: arising from cells in the CNS Secondary: arising from the spread of cancerous cells from another site in the body
The most common cancers to metastasize to brain are lung, breast, and melanoma CNS involvement can be the 1st sign of a cancer in the body CNS TUMORS In the CNS, many different kinds of cells can give rise to primary tumors; more common of these types include: Meningiomas: arise from meningeal cells; most common primary tumor in CNS Gliomas: derived from cells that in development arise from glioblasts (immature cells that give rise to glial cells in the brain) Ependymomas: arise from ependymal cells that line the ventricles
Oligodendrogliomas: arise from oligodendrocytes; generally slow-growing and benign Astrocytomas: arise from astrocytes; the most common glial cell tumor in adults There are a number of genetic risk factors; risk with age and where you live; the only environmental risk factor identified is exposure to ionizing radiation, particularly when young CNS TUMORS Brain tumors may be Benign: non-cancerous; the vast majority (~85%) of meningiomas are benign; slow-growing, non-invasive
Malignant: cancer; fast-growing and invasive While brain tumor cells rarely metastasize to other parts of the body, they may metastasize within the brain CNS TUMORS Tumors can also be graded by their malignancy For example, Astrocytomas are graded from I- IV (low-grade to high-grade); low grade are minimally invasive and slow-growing High-grade (IV): tumors are rapidly growing, invasive (the cells invade adjacent normal tissue), and undifferentiated
(cells look immature and in various stages of cell division); Grade IV astrocytomas are also called glioblastoma multiforme (GBMs) High-grade astrocytomas can arise de novo (primary) or evolve from low-grade astrocytomas (secondary) WHY THERE ARE NO NEURON TUMORS IN THE ADULT CNS In development, Glioblasts give rise to oligodendrocytes, ependymal cells and astrocytes; all of
these cell types are capable of mitosis (cell division to create new cells) throughout life Oligodendrocytes Mitotic Non-mitotic Neuroblasts give rise to neurons; neurons are postmitotic cells, meaning that
they are not capable of cell division in adults; thus, they do not form tumors in the adult brain CNS TUMORS CNS TUMORS MAY PRODUCE BOTH GENERALIZED AND LOCALIZED SIGNS/SYMPTOMS GENERALIZED SYMPTOMS WOULD INCLUDE HEADACHE, SEIZURES, CONFUSION LOCALIZED SIGNS/SYMPTOMS DEPEND ON WHERE THE TUMOR IS; ADDITIONAL SIGNS/SYMPTOMS WILL BE SEEN
AS THE TUMOR GROWS AND EXPANDS TO INVOLVE NEARBY AREAS IN GENERAL, ONSET OF SIGNS/SYMPTOMS IS PROGRESSIVE In infants and small children, tumors can arise from immature cells Blastoma: neoplasms which are composed of immature, undifferentiated cells Medulloblastoma: a highly malignant cancer occurring primarily in infants/young children; named because the tumors are composed of immature cells that look like primitive cells of the medullary area of the developing
neural tube Most commonly occur in the vermis (midline area) of the cerebellum a structure involved in balance, equilibrium, and coordination of learned, skilled motor movement ALL BRAIN TUMORS ARE POTENTIALLY LIFETHREATENING BECAUSE OF THE POSSIBILITY OF BRAIN HERNIATION Herniation of the brain can cause death; for example, tonsillar herniation produces pressure on cardiovascular and respiratory centers in the medulla, causing death
BRAIN TUMORS While tumors can occur in the spinal cord, we will confine our discussion to brain tumors reinforcing that understanding the functional anatomy of the brain is the key to understanding how physicians come to an anatomic diagnosis Our discussion of Clinical Cases will involve 4 types of tumors:
Medulloblastoma Meningioma Glioblastoma multiforme Astrocytoma CLINICAL CASE I Cindy is a 28 month old girl, brought to the pediatrician by her Mother who was concerned because the little girl was falling frequently and seemed to have very poor balance. The problems had been present since Cindy had begun to walk (at 13 months), and were getting progressively worse;
the child had also become increasingly irritable and withdrawn. The Mother also reported that the child vomited frequently. Upon examination, Cindy was seen to have a broad-based ataxic gait; she required help in sitting, standing, or walking Medulloblastoma Tumor cells in the midline of the cerebellum; causes Wide-based gait, ataxia, and truncal instability
Nausea and vomiting probably secondary to increased intracranial pressure, as well as pressure on medulla from expanding tumor WHY MEDULLOBLASTOMA IS SO DANGEROUS It is a malignant cancer Often not diagnosed early, because infants are naturally ataxic (uncoordinated) Most common site is the midline area of the cerebellum which
is close to the 4th ventricle (one of the cavities in the brain that contains Cerebrospinal Fluid [CSF]); malignant cells get into CSF and seed to other areas of the brain 4th ventricle can also be blocked by cancer cells and a hydrocephalus (build-up of CSF in ventricles) can occur which can also cause the brain to herniate WHY MEDULLOBLASTOMA IS SO DANGEROUS 4th Ventricle MENINGIOMA
Most common primary brain tumor (~30% of all brain tumors) in adults Generally, slow-growing benign (~85%) tumors Meninges (connective tissue sheaths that surround the brain and spinal cord), from outer to inner DURA ARACHNOID PIA CLINICAL CASE II A 47 yo Caucasian woman (Mrs. T. D.) goes to her gynecologist
for her yearly examination. She tells the gynecologist that over the last year she has been having headaches and depression. No neurological exam was deemed necessary on the assumption that her headaches and depression were due to perimenopause. Two months later, Mrs. D. was found unconscious by her husband and brought into the Emergency Department by ambulance. He reports that she had been having severe headaches and had been very depressed and difficult to get along with over the last few months. MENINGIOMA
MENINGIOMA of the left frontal lobe Depression was the result of compression of the left frontal lobe; headaches and death were due to increased intracranial pressure and eventual herniation of the brain GLIOBLASTOMA MULTIFORME Glioblastoma multiforme (GBMs) are highly malignant tumors (Grade IV astrocytomas); they are rapidly growing, invasive, with undifferentiated
cells CLINICAL CASE III A 69 yo African-American male professor (Mr. D. M.) at a major medical school has a seizure during a departmental faculty meeting. He is immediately taken to the Emergency Department where an emergent CT shows a mass in his right hemisphere involving the frontal/parietal lobe area/underlying axons. Consultation with neurosurgery indicates that the tumor is inoperable because of how it has invaded surrounding tissue; thus, surgery would require the
resection or removal of a large amount of normal tissue. Chemotherapy and radiation were begun in order to shrink the tumor mass and to try and slow the tumor growth. CLINICAL CASE III, Cont. The initial neurological examination revealed Papilledema (Due to increased intracranial pressure) Weakness on the left (Involvement of primary motor cortex [Area 4]/underlying axons on the right) Loss of fine touch, vibration and conscious proprioception on the left (Involvement of primary somatosensory cortex
[Areas 3, 1 & 2]/underlying axons on the right) When asked if he was experiencing headaches he said yes and that they were worse in the mornings CLINICAL CASE III, cont. Normal fundus Appearance of fundus under conditions of increased intracranial pressure (papilledema)
CLINICAL CASE III, Cont. Areas 3, 1 & 2 primary somatosensory cortex Area 4 primary motor cortex A tumor is compromising Areas 4 and 3, 1 & 2, and underlying axons
Mr. M. has headaches that are worse in the mornings because of the redistribution of CSF (in the presence of a tumor), when going from a lying down to a standing position CLINICAL CASE III, Cont. After chemotherapy and radiation, Mr. M. had a few good months. He then developed (in addition to previous signs/symptoms) Contralateral (left-sided) neglect (Due to growth of the tumor to include posterior parietal cortex/underlying
axons on the right) CLINICAL CASE III, Cont. CONTRALATERAL (LEFT) NEGLECT Posterior Parietal Cortex Tumor has expanded to now include posterior parietal cortex/ underlying axons, causing contralateral (left) neglect of the body & world; also extends to memory
CLINICAL CASE III, Cont. CONTRALATERAL NEGLECT CLINICAL CASE III, Cont. Note how the tumor has invaded normal tissue so that it is difficult to tell the difference between normal tissue and the
tumor CLINICAL CASE IV Astrocytoma A 47 yo Caucasian male (Mr. R. W.) goes to his Primary Care Physician for his yearly wellness visit. During the neuro portion of his physical examination, the physician notes that Mr. W. has lost his sense of smell, and that he has a grasp reflex. After being referred to a Neurologist, a CT is done and a large tumor is identified in the anterior cranial fossa.
CLINICAL CASE IV, Cont. CT WITH CONTRAST (Tumors lack a blood-brain barrier which is why this tumor is showing up bright white when a contrast agent is given) CLINICAL CASE IV, Cont. The tumor is at the base of the brain, anteriorly The tumor crosses the midline and has affected both frontal lobes and olfactory structures FRONTAL
LOBE The brain is upside down so that the ventral underside of the brain is visible; the blue circle indicates the extent of the tumor FRONTAL LOBE
OLFACTORY BULBS CLINICAL CASE IV, Cont. The loss of smell (anosmia) is because the olfactory bulbs have been affected bilaterally The grasp reflex is a reflex seen normally in infants; it is inhibited by the frontal lobe during development; thus, the re-appearance of the reflex in an adult is a pathological sign; it signals compromise of the prefrontal cortex
CLINICAL CASE IV, Cont. Mr. W. had surgery to remove the tumor; he has done well. He does show persistent anosmia (they were unable to save the olfactory bulbs) and difficulty inhibiting his behavior. The latter is due to damage to the prefrontal cortex which occurred both because of the tumor and its removal. Post-surgical MRI; area where the tumor was removed is filled with CSF TAKE-HOME MESSAGES
If you or a loved one experience progressive headache, confusion, memory loss, loss of function (motor, sensory, etc), or other events (like a seizure), notify your Primary Care Physician! If a brain tumor is identified, survival depends on many factors but early diagnosis is important if surgery is an option Also remember: CNS involvement could be the 1st sign of a cancer in the body again early detection is important!
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