Associate Professor Division of Neurosurgery, Department of Surgery Faculty of Medicine Siriraj Hospital, Mahidol University
Original Thai edition: ISBN 974-7445-46-8
This English edition currently contains Chapter 1, corresponding to pages 1–15 of the Thai original. The original illustrations and reference numbering are retained. This is a draft translation of the author's work, not an English text written by the author. The Thai text remains the reference for checking the translation.
English translation in preparation
Original publication details
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
Front matter; Chapters 1–2, pages 1–53; and part of Chapter 3, pages 126–149 and 174–183. Chapter 3 pages 54–125 and 150–173 and Chapters 4–7 are still being prepared.
Original printed pages 1–6
Chapter 1 · Introduction
Brain Tumors
Tumors arising within the brain are an important form of pathology. They are classified as intracranial expanding lesions and cause loss of brain function according to their location. Patients may present with a variety of neurological symptoms. When a tumor becomes large, it raises intracranial pressure and may ultimately cause death. A patient's survival therefore depends in part on the physician's knowledge, experience, and ability to diagnose the disease at an early stage and provide appropriate treatment in time. Most brain tumors arise from cells of the tissues that make up the brain (primary brain tumors), while a smaller proportion spread from cancers of other organs (metastatic brain tumors). Primary tumors may be either malignant or benign. Their nomenclature and classification are discussed in the next chapter.
Brain tumors can, in fact, arise anywhere within the cranial cavity. Experience and reported statistics nevertheless show that many types have characteristic sites of origin. Meningiomas, for example, favor the parasagittal region, the lesser wing of the sphenoid, the olfactory groove, and the tuberculum sellae. Craniopharyngiomas occur in the suprasellar region, and medulloblastomas arise in the cerebellar vermis. Each type also has a characteristic age range and an age at which it occurs most frequently. The relationship between preferred location and age is clinically important because it helps distinguish one tumor type from another.
Causes of Brain Tumors
As with tumors elsewhere in the body, the precise cause of most brain tumors is unknown. However, several factors can contribute to their development:
1. Abnormal development of embryonal cells
This is one cause of tumors, particularly those found in children. Normally, cells develop into parts of the brain with different functions. Some cells may remain as embryonic rests and subsequently grow abnormally to form brain tumors, most of which lie in the midline. Common examples include dermoids, epidermoids, teratomas, craniopharyngiomas, chordomas, and medulloblastomas. Craniopharyngiomas in the pituitary region arise from remnants of the craniopharyngeal duct left during formation of the pituitary gland. Chordomas arise from notochordal remnants. Medulloblastomas were attributed to remnants of the primitive external granular layer of the cerebellum,(1) but are now believed to arise from primitive neuroectodermal tissue.(2)
2. Hereditary factors
Three hereditary disorders associated with brain tumors belong to the phakomatoses, a group of inherited abnormalities affecting the skin, eyes, and nervous system:
von Recklinghausen's neurofibromatosis;
tuberous sclerosis (Bourneville's disease);
von Hippel–Lindau disease.
Von Recklinghausen's neurofibromatosis, known in Thai as “โรคท้าวแสนปม,” is a clear example of an inherited disorder involving tumors of the nervous system. Several members of the same family may be affected. Tumors may occur in the brain, peripheral nerves, and skin. Among intracranial tumors, acoustic neurinoma is the most common; meningiomas and gliomas, including optic nerve gliomas, may also occur. Bilateral acoustic neuroma, or bilateral acoustic neurofibromatosis, is hereditary and has a gene distinct from that associated with peripheral neurofibromatosis.(3) In affected families it is transmitted as an autosomal dominant trait, and affected individuals develop acoustic neuromas on both sides. This differs from nonhereditary acoustic neuroma in that symptoms and signs appear during adolescence, whereas the nonhereditary form usually presents between 40 and 50 years of age.
Tuberous sclerosis is another hereditary disorder that causes abnormalities in the brain and elsewhere in the body. Important diagnostic features are: i) adenoma sebaceum on the face on either side of the nose, in the “butterfly area” (Figure 3.11); and ii) subependymal giant cell astrocytomas along the walls of the lateral and third ventricles. These are usually small nodules, although some may be large (Figure 3.12). The cerebral surface may show nodules (tubers), gliotic cortical plaques, and macro- or microgyria. These abnormalities cause seizures and intellectual disability.
Von Hippel–Lindau disease is an autosomal dominant hereditary disorder(4) involving benign capillary hemangioblastomas together with retinal angiomas. Cerebellar hemangioblastoma is the most common intracranial tumor and may occur as a solitary or multiple lesion. Associated abnormalities in other organs include pancreatic and renal cysts and hypernephroma. The author has encountered this disease in four siblings from the same family.
3. Brain injury
Brain injury has long been suspected as a factor or cause in the development of tumors of the meninges and glial cells, but this has not been clearly proved. Reports describe tumors at sites of previous injury, yet such cases are very rare in relation to the total number of tumors. Cushing and Eisenhardt,(5) however, considered brain injury an important factor in meningioma development. Of their 313 patients, 33% had a history of brain injury; in 24 of these cases the tumor lay at the site of a depressed skull fracture and a scar on the cerebral surface. Other reports have also described tumors at sites of brain injury, chiefly meningiomas. Tumors of neuroepithelial tissue or glial cells are less common in this setting. Most post-traumatic tumors develop many years after the injury. Zülch proposed that, following injury, meningeal or glial cells regenerate abnormally and become a focus of tumor formation.(6)
These tumors may give rise to legal questions. Zülch(7) proposed the following criteria for considering a brain tumor causally related to a brain injury:
The patient must have been normal before the injury.
The head injury must have been severe enough to damage the brain and meninges and initiate chronic regenerative processes.
The tumor's location must correspond to the site of brain injury.
A sufficiently long interval must separate the injury and development of the tumor. The interval may vary, but development within two or three weeks is unlikely; most such tumors arise years after injury.
The tumor must be established histologically. This may be problematic: a cerebral scar, for example, may be histologically indistinguishable from a low-grade astrocytoma.
4. Radiation
It has long been known that irradiation of the central nervous system can later cause brain necrosis at the irradiated site.(8) It may also cause tumors, including fibrosarcoma, meningioma, astrocytoma, and glioblastoma multiforme. Of these, fibrosarcoma has been reported most frequently. The mechanism by which radiation causes brain tumors remains unexplained. To attribute a tumor to radiotherapy, it must occur within the irradiated area after a sufficiently long interval, generally between 5 and 12 years.(9) The latency is related to the radiation dose: the higher the dose, the shorter the interval before tumor development.
Fibrosarcoma has been reported after radiotherapy for pituitary tumors.(10) Russell and Rubinstein also reported a patient with a well-circumscribed giant-cell glioblastoma of the frontal lobe that was completely removed. Six years after radiotherapy, a dural fibrosarcoma developed at the operative site.(11) Zülch(12) found a fibrosarcoma at an irradiated site six years after treatment of a hemispheric ependymoma.
Meningiomas have been reported after radiotherapy for pituitary tumors, glial tumors, and scalp disorders. Iacono and colleagues(13) reported multiple meningiomas following radiotherapy for medulloblastoma.
Modan and colleagues(14) reported a statistically significant study of 10,902 Israeli children treated with radiation for tinea capitis. Comparison with children who had not received radiation, 12–23 years later, showed a fourfold higher occurrence of meningioma in the irradiated group.
In 1988, Ron and colleagues(15) followed 10,834 patients who had received radiotherapy for tinea capitis. Brain tumors were 8.4 times more frequent in the irradiated group than in the unirradiated group. Most were meningiomas, gliomas, or nerve sheath tumors.
5. Immunological disorders
Immunosuppression is now known to play an important role in tumor development after organ transplantation. Some patients who undergo renal transplantation with complete immunosuppression subsequently develop brain tumors, chiefly lymphomas and sarcomas.(16),(17)
Three groups are at risk of developing non-Hodgkin's lymphoma of the central nervous system: i) organ transplant recipients; ii) patients with AIDS; and iii) patients with congenital immunodeficiency syndromes. Among these lymphomas, the proportion occurring in kidney and heart transplant recipients has been reported as high as 30%.(16)
6. Viruses
Viruses can cause brain tumors in experimental animals. Their role in humans remains uncertain, and it has not been proved that viruses cause human brain tumors. However, virus-like particles have been found within brain tumors.
7. Chemicals
No chemical is currently known to be a cause of brain tumors in humans. Nevertheless, several chemicals, including ethyl- and methylnitrosourea, can cause nervous system tumors in experimental animals.(19) Methylcholanthrene, anthracycline, and other anthracene derivatives can also produce nervous system tumors.
Original printed pages 6–9
Incidence of Brain Tumors
The reported incidence of different brain tumor types varies, in part according to whether the figures come from neurosurgical operations or neuropathological autopsies. A surgeon's particular expertise in operating on certain tumor types or locations may affect the statistics. Referral centers receiving patients from other hospitals for surgery will also report higher numbers. Other factors contributing to differences include:
1. Classification of brain tumors. The brain contains various neural elements, including glia, neurons, and cranial nerves, as well as the meninges, pituitary gland, and pineal gland. Cells in these structures can give rise to tumors. Brain tumors have long been classified according to their histopathological characteristics and biological behavior. Several systems have been used, including those of Kernohan and Sayre, WHO (see Chapter 2), and Zülch. They differ in some respects, and the names of certain tumors have also changed. These factors make comparisons of incidence difficult.
2. Heterogeneity within a tumor. Some brain tumors, such as malignant gliomas, show different degrees of malignancy in different areas. One area may resemble a low-grade astrocytoma, while areas showing necrosis and vascular proliferation represent high-grade astrocytoma. Examination of a small biopsy may therefore misrepresent the degree of malignancy and distort incidence figures. The true degree of malignancy must be assessed from the entire tumor or at autopsy.
In some cases a glioma becomes more malignant with time. In the author's experience, this has often been observed at a second or third operation.
3. Autopsy rates. These differ between institutions. A hospital with a high autopsy rate has a greater opportunity to detect brain tumors that have not yet caused symptoms.
4. Tumor location. Tumors in critical locations, such as the brain stem, sometimes cannot be sampled for examination and are diagnosed using CT and MRI. The appearances on these studies are not specific to brain tumors, so the diagnosis may be mistaken. A ring-shaped lesion, for example, may be a brain abscess, metastatic tumor, or glioblastoma.
Despite these variations, a review of published reports(20, 22, 23, 24, 25, 26) indicates that gliomas are the most common brain tumors (40–50%), followed by meningiomas (15–20%), acoustic neurinomas, pituitary adenomas, and metastatic tumors, in that order. The reported incidence of metastatic tumors varies considerably depending on whether the data come from autopsy or surgery. Lung cancer is the most common primary source of brain metastases, followed by cancers of the breast, gastrointestinal tract, and kidney. In 60–80% of metastatic brain tumors, lesions are found at multiple sites within the brain.
The incidence of each tumor type at different ages and locations is important because it contributes to the diagnosis. Some tumors occur only in children and are not found in adults, while others occur in adults but not in children. The patient's sex is less important than age and location.
Age Incidence
The precise age at which a tumor begins cannot be determined, because early tumors do not cause symptoms. Reported age therefore means the patient's age at hospital admission or, for an untreated patient, at death. All types of brain tumor may occur at any age, but most occur from approximately the end of the first decade through middle age. They are less common before age ten and after age seventy. Tumors frequently seen in young children and adolescents include gliomas of the cerebellum, brain stem, optic nerve, and hypothalamus; craniopharyngiomas; pinealomas; teratomas; and medulloblastomas, described here as tumors occurring specifically in children within the first decade of life.
The number of brain tumors occurring in childhood decreases during adolescence, gradually rises again in middle-aged adults, and falls once more in old age.(27)
Common tumors in middle age include meningiomas; gliomas of the cerebral hemisphere, particularly glioblastoma multiforme; acoustic schwannomas and other cerebellopontine angle tumors; and pituitary adenomas. Metastatic tumors tend to occur in later middle age.
In old age, most tumors are glioblastomas, meningiomas, acoustic schwannomas, or metastatic tumors.
Studies show that each tumor type not only occurs across different age ranges but also has a different age of peak incidence, as shown in Table 1.1.
Table 1.1. Age ranges and peak incidence of brain tumors. Black bars: age range in which the tumor occurs. White segments: the most frequent age range. The original chart is retained; the Thai axis label means “Age,” and the two Thai legend labels correspond to the descriptions above.
Original printed pages 9–13
Preferred Locations of Brain Tumors
Tumor location is important for both diagnosis and prognosis. Different locations present different degrees of difficulty, risk, and complications in surgical treatment, with corresponding differences in outcome. A tumor on the cortical surface is easier to remove than one adjacent to the brain stem.
In a study of 510 patients of all ages who underwent surgery for brain tumors, most tumors were supratentorial (66.3%), while 37.7% were infratentorial. Approximately two-thirds of supratentorial tumors lay in the cerebral hemispheres, including the basal ganglia and lateral ventricles. The remaining third occurred in the pituitary fossa, diencephalon, third ventricle, or pineal gland. Within the hemispheres, the frontal lobe was the most common site and the occipital lobe the least common. The parietal and temporal lobes were affected in approximately equal numbers. The higher frequency in the frontal lobe may reflect its larger volume of brain tissue, whereas the smaller occipital lobe offers less opportunity for tumor development.
Of infratentorial tumors, approximately half were in the cerebellum and fourth ventricle, another 20% in the brain stem, and 30% outside the brain stem in the cerebellopontine angle, foramen magnum, clivus, or tentorium.
An important difference between childhood and adult brain tumors concerns their location. Approximately 60–70% of childhood brain tumors are infratentorial and 40% supratentorial. In adults, approximately 60% are supratentorial.
In children within the first decade of life, the most common infratentorial tumor is cerebellar medulloblastoma. It arises in the posterior velum of the fourth ventricle, grows in the cerebellar midline, and extends into the fourth ventricle and cerebellar hemispheres. Next in frequency are ependymoma of the fourth ventricle and cerebellar astrocytoma. During adolescence, however, cerebellar astrocytomas become more frequent, while medulloblastomas and ependymomas become less frequent. Astrocytomas usually lie in the cerebellar hemispheres and are most often benign cystic astrocytomas. Pilocytic astrocytomas also favor the brain stem in children under ten. Cerebellar hemangioblastomas, acoustic neurinomas, and meningiomas are not found in young children and occur predominantly in middle-aged adults.
Other brain tumor types and their preferred locations at different ages in children and adults are summarized in Figures 1.1 and 1.2.
Figure 1.1. Types and locations of brain tumors in children.
Meningiomas occur in middle-aged adults and have characteristic preferred locations. They are commonly found along the cerebral convexity, falx and parasagittal region, olfactory groove, tuberculum sellae, tentorium, petrous ridge (Figure 1.3), and foramen magnum. Intraventricular meningiomas and those involving the optic nerve sheath and canal are less common.
Figure 1.3. Common intracranial locations of meningiomas.
Original printed pages 12–14
Changes in the Brain Caused by Tumors
A brain tumor produces two important types of change in the brain:
1. Brain edema around the tumor (Figure 1.4). Compression of arteries and veins slows arterial flow and obstructs venous drainage, causing hypoxia in the surrounding brain and disruption of the blood–brain barrier. During surgery, the capillaries can be seen to be compressed and narrowed, while the brain appears pale and swollen.
Edema also depends on the nature, type, size, and location of the tumor. Different tumors have different toxic effects on the brain and therefore cause varying degrees of edema. Malignant tumors, such as metastatic tumors, glioblastoma multiforme, sarcomas, and lymphomas, may cause extensive swelling. A characteristic feature of metastatic tumors is marked edema even when the tumor itself is small (Figure 1.4). In contrast, infiltrating gliomas such as grade I and II astrocytomas and oligodendrogliomas produce very little change in the surrounding brain, and edema is uncommon. Meningiomas likewise generally cause little surrounding edema, except those in the parasagittal region or sphenoid wing, or those that are very large. These frequently produce marked edema, which can be explained by disruption of venous circulation.
Figure 1.4. Edema of the brain surrounding a tumor. 1. Tumor. 2. Brain edema.
In general, tumor size alone seldom causes a very large rise in intracranial pressure. A marked and rapid rise usually results from the combined effects of four abnormalities: the tumor itself, brain edema, obstruction of cerebrospinal fluid pathways, and venous congestion. If the tumor does not obstruct cerebrospinal fluid flow, peritumoral edema is the most important factor causing focal loss of brain function and symptoms of raised intracranial pressure. The more rapidly edema develops, the more rapidly brain function, including the level of consciousness, deteriorates.
2. Displacement effect. Compression by the tumor and increased intracranial pressure displace brain tissue from areas of higher pressure toward areas of lower pressure, producing herniation at various sites, as discussed in a later chapter. These changes in turn progressively increase edema through ischemia and impair the function of other parts of the brain, particularly the vital structures of the brain stem.
Original printed pages 14–15
References · Chapter 1
Bibliographic entries retain the wording and numbering of the original edition.
Matson D.D.,: Tumors of posterior fossa, in Neurosurgery of infancy and childhood, Charles C. Thomas Pub. p 448-449, 1969.
Rorke L.B.,: The Cerebellar Medulloblastoma and Its Relationship to Primitive Neuroectodermal Tumors. J. of Neuropath. and Experiment. Neurol. Vol. 42, pp 1-15, 1983.
Kanter W.R., Eldrige R., Fabricant R., Allen J.C., Koerber T.: Central neurofibromatosis with bilateral acoustic neuroma : Genetic, clinical and biochemical distinction from peripheral neurofibromatosis. Neurology (N.Y.) 30 : 851-859, 1980.
Horton W.A., Wong V., Eldridge R.,: Von Hippel-Lindau disease. Arch. Internal Med. 136 : 769-777, 1976.
Cushing H., and Eisenhardt, L., : Meningiomas : Their classification, Regional behavior, Life, History, and Surgical end results, Springfield, Ill. Charles C. Thomas, 1938.
Zulch K.J. and Mennel H.D., : Biology of brain tumors in Tumors of the Brain and Skull Ed. by Vinken P.J. and Bruyn G.W. North-Holland Pub. Co., vol. 16 : 1-55, 1974.
Zulch K.J., : The origin of brain tumors. In Brain tumors, their biology and pathology, Springer Verlag pp. 76-77, 1986.
Bouchard, J., Radiation Therapy of Tumors and Diseases of the Nervous System, Lea & Febiger Pub. pp. 31-42, 1966.
Walker J.S., Bigner D.D., Radiation-induced brain tumors in Neurosurgery ed. by Wilkins R.H. and Rengachary, Mc Grawhill Co. pp. 525-527, 1985.
Waltz TA, Brownell B. : Sarcoma : A possible late result of effective radiation therapy for pituitary adenoma : Report of 2 cases J. Neurosurg. 24 : 901-907, 1966.
Russell D.S., and Rubinstein, L.J. : Pathology of Tumors of the Nervous System 2nd Ed. London, Arnold, 1963.
Zulch K.J. : Brain Tumors. Their Biology and Pathology 2nd Ed. N.Y. Springer Verlag, 1965.
Iacono R.P., Apuzzo M L J, Daves RL, Tsai Fy : Multiple meningiomas following radiation therapy for medulloblastoma : Case report. J. Neurosurg. 55 : 282-286, 1981.
Modan, B., Baidatz, D., Mart, H., Steinitz, R., and Levin, S.G., Radiation induced head and neck tumors. Lancet 1 : 277-279, 1974.
Ron, E., Modan B., Boice J.D., Alfandary, E., Stovall, M., Chetrit, A., and Katz, L. Tumors of the brain and nervous system after radiotherapy in childhood N. Engl. J. Med. 319, 1033, 1988.
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Hoover R., Fraumeni J.F. : Risk of cancer in renal transplant recipients. Lancet II : 55-57, 1973.
Hochberg F.H., Gabbai A.A., Risk factors in development of glioblastoma and other brain tumors in Neurosurgery Update I by Wilkins RH & Rengachary SS. p. 242-243, 1990.
Wechsler, W., Kleihues, P., Matsumoto, S., Zulch K.J., Ivankovic S., Preussmann, R., and Druckrey H. : Pathology of experimental neurogenic tumors chemically induced during prenatal and postnatal life, Ann. N.Y. Acad. Sci., 159 : 360-408, 1969.
Schoenberg, B.S., Christine, B.W., and Whisnant, J.P., The descriptive epidemiology of primary intracranial neoplasms : The Connecticut experience. Am, J. Epidemiology. 104, 499., 1976.
Walker, A.E., Robins, M., and Weinfeld F.D., Epidemiology of Brain tumors : The National Survey of Intracranial Neoplasms. Neurology, 35 : 219, 1985.
Heshmat, M.Y., Kovi, J., Simpson, C., Kennedy, J., and Fan, K.J., Neoplasms of the central nervous system : incidence and population selectivity in the Washington D.C. Metropolitan area. Cancer. 38, 2135, 1976.
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Cheng, M.K., Brain tumors in the People’s Republic of China : A statistic review. Neurosurgery, 10, 16, 1982.
Wen-Qing, H., Shi Ju. Z., Qing-Sheng, T., Jian-Qing, H., Yu-xia, L., Qing-Zhong, X., Zi-Jun, L., and Wen Cui, Z., Statistical analysis of central nervous system tumors in China J. Neurosurg. 56, 555, 1982.
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English translation in preparation
Chapter 2 · Classification of brain tumors
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
This section has not yet been translated into English. You can read the Thai original at the same section, or choose a translated part of Chapter 1 from the contents.
