NEUROLOGY
Malignant Gliomas Some
W. H. Brooks, M.D.,*
~~ LIC3~~~S’ acteristically
of
Diagnostic Comments
Joseph
C. Parker, Jr., M.D.,** A. B.
&dquo;the optic pathway char-
in childhood, with a peak incidence between two and six years These gliomas, comprising less than 1 per cent of all aliomaS,3 are frequently not considered in the differential diagnosis of central nervoccur
ous
system
tumors.
these lesions can be divided into distinct groups, each having its own characteristic behavior. Gliomas which originate in that portion of the optic nerve which is in the orbit extend through the optic foramen and characteristically present with proptosis and failing vision. Since they do not give rise to extraocular muscle palsies, they are easily differentiated clinically from the other more malignant tumors of this region which originate from the ocular muscles or the bony orbit. Generally, optic nerve gliomas in this region do riot present a diagnostic problem and furthermore hold
Clinically,
two
*
Assistant Professor, Division of Neurosurgery, UniMedical Center, Lexington, Ky. Associate Professor and Director of Neuropathology, Department of Pathology. t Assistant Professor, Division of Neurosurgery. &Dag er; Assistant Professor, Division of Neurosurgery. Correspondence to W. H. Brooks, M.D., Division of Neurosurgery, University of Kentucky Medical of Kentucky versity **
Center,
Lexington, Ky. 40506.
of the Optic Chiasm in Adolescents Based on Experiences with Two Patients
Young, M.D.,†
R. H. Mortara,
M.D.‡
good prognosis.’ Unfortunately, they acfor only one-third of the gliomas occurring within the optic pathway. The more commonly occurring lesions arise intracranially from the optic chiasm. They have a quite different and varied clinical presentation, which makes their precise diagnosis more challenging. The purpose of this presentation is to illustrate the difficulty in diagnosing these optic pathway gliomas, particularly during adolesa
count
cence
when endocrine abnormalities and features of the tumor are promi-
malignant nent.
Case
Reports
Case 1. A 13-year-old girl had a four-month of visual loss, polydipsia, polyuria, and headache. Measurements showed her to be in the tower 10 percentile range of normal height and weight. No other physical abnormality was evident. Neurologic examination showed optic atrophy with marked limited visual acuity and abnormal peripheral vision (Fig. 1). Blood count, blood chemistry studies, and urinalvses were all normal. Plasma cortisol, PBI, T;¡, T~, TSH, LH, and GH assays indicated panhypopituitarism. Skull films demonstrated suprasellar calcification (Fig. 2). Cerebral angiography depicted no vessel displacement or circulatory alteration. Conray ventriculogram illustrated blunting and
history
557
FIG. 1. Nonspecific defects in the peripheral vision of Cases I and 2 as determined by tangent screen
elevation of the floor of the anterior third ventricle by a suprasellar mass, presumedly a
craniopharyngioma (Fig. 3). Operative exposure revealed a markedly hypertrophied and gray optic chiasm consistent with a malignant glioma. Calcification was noted within the arachnoid covering the chiasm. There was no evidence of tumor extending into the third ventricle or within the sella. A biopsy from the
posterior portion
perimetry.
of the chiasm
scanty tissue and demonstrated
yielded very only lymphoid
cellular infiltrates and fibrous tissue consistent with reactive changes to an adjacent malignant glioma. No neuroglial tissue was seen. Despite 5500 R to the chiasmatic region, the patient’s vision has progressively deteriorated. She is presently blind with severe hypothalamic dysfunction. Case 2. A 20-year-old girl was admitted with
FIG. 2. The suprasellar calcification noted in Case 1 suggested the presence of a craniopharyngioma.
558
FIG. 3. Conray ventriculogram indicating a mass lesion in the region of the optic chiasm-hypothalamus.
history of amenorrhea, weight gain, personality change, polvdipsia, and p«lyul&dquo;ixz. Except for obesity, the physical examination was normal. Neurologic examination showed hilateral optic atrophy, limited vistzal acuity and abnormal peripheral vision (Fig. 1). The usual routine laboratory tests were normal. Plasma cortisols, a
one-year
PBI, T3’ T4, TSH, LH, and GH assay results indicated panhypopituitarism. Skull x-rays sugan enlarged sella. Cerebral angiography normal. Pneumoencephalography illustrated absence of filling of the anterior third ventricle similar to the first patient. The preoperative diagnosis was a craniopharyngioma or a chrazrzaphobe adenoma. At operation, the optic chiasm was hypertrophied. Biopsy yielded scanty tissue which contained malignant astrocytes, prominent and leptomeningeal perivascular lymphoid cellular infiltrates (similar to Case 1), and atypical gemistocytes diagnostic of a moderately differentiated (grade II) astrocytoma (&dquo;astroblastoma&dquo;). The patient has become worse despite radiation therapy and is presently moribund.
gested
was
Discussion These cases clearly demonstrate the difficulties in recognizing an optic chiasm lesion from clinical and radiologic studies. Both presented with endocrinopathic symptoms which suggested a sellar or suprasellar lesion but did not specifically indicate a
chiasmal glioma. Three important features of cases of this type warrant discussion.
Hypothalamic-Pituitary The
occurrence
of
Dysfunction
hypothalamic dysfunc-
is unusual as an initial Such involvement of the presentation.2,4-6 axis hypothalamic-pituitary by chiasmal gliomas was initially observed l~y Martin and Cushin_.7 Reviewing the Mayo Clinic experience, Dodges al.~ noted that only 9 of 46 patients with optic nerve gliomas exhibited endocrine abnormalities. Those that arose intracranially were associated with increased intracranial pressure. The endocrinopathies in their cases appeared late in the disease and were mild .6 When hypothalamic dysfunction develops in adults with malignant chiasmatic gliomas, it is usually late and death is imminent.5 Hypothalamic dysfunction associated with chiasmal gliomas is caused by direct compression and extension of the tumor into the hypothalamic region or through its compromising of the vascular supply. In our cases, since operative inspection indicated no direct tumor extension or infundibular compression, vascular obstruction and the subse-
tion,
as
in
Axis
our cases,
559
quent ischemia was likely responsible the endocrinopathy.
for
Radiologic Findings Routine skull examinations show abnormal findings in about 75 per cent of the patients with gliomas which arise in the orbit and extend through the optic foramen. In contrast, the x-rays are frequently normal in patients with intracranial gliomas arising in the optic chiasm.1,11 The customarily described radiographic findings of the former type of optic gliomas are asymmetrical enlargement of the optic canal and a so-called &dquo;J&dquo; or &dquo;gourd&dquo; shaped sella.1,2,4,6,7,13 Though
strongly suggestive, these findings are not pathognomonic because 20 to 25 per cent of normal individuals have slight asymmetric enlargement of one of the optic foramina. Therefore, only gross asymmetry with or without rounding of the usual rectangularshaped canal should be deemed abnormal. A &dquo;J&dquo; shaped sella is less specific; it may be found in children with various other pathologic conditions’ as well as in some normal infants. The rare and misleading radiographic feature of suprasellar calcification noted on the lateral skull x-rays of Case 1 deserves emphasis. Such calcification in a child sug-
gests
a
craniopharyngioma,1,10 particularly
when in conjunction with hypopituitarism and visual field defects. Cushingil and Bailey&dquo; have described instances of suprasellar calcification within an optic nerve glioma. Since their patients had no endocrine abnormalities, the presence of a craniopharyngioma was not suspected as in our case. Cerebral angiography may help in defining larger tumors and in excluding vascular
Loss of the normal
configuration of the anterior third ventricular recesses, obliteration of the chiasmatic cistern, and outline of the tumor within the interpenduncular cistern can usually be well demonstrated. But when the tumor is confined to the orbit, pneumoencephalography gives normal findings. Pathology Gliomas that arise within the optic nerve of children appear to have different features from those found in adolescents and adults. The &dquo;classical&dquo; childhood optic nerve gliomas usually have limited growth potential and their course resembles that of a hamartoma.~ Malignant degeneration usually does not
develop, so that the prognosis is good even with biopsy or partial resection.’ 2,4,6,8 The gliomas observed in our patients were similar to chiasmatic gliomas appearing in adulthood.5 Histologically, one tumor demonstrated pleomorphic malignant changes suggestive of an aggressive neoplasm. Final Comments From the records of our patients and a survey of the literature, two conclusions can be reached. First, a chiasmatic glioma must be considered in the differential diagnosis of hypothalamic-pituitary axis dysfunction even when suprasellar calcification may be demonstrable. Secondly, gliomas of this region in adolescent patients are not necessarily hamartomatous in nature and should not be considered benign lesions without a surgical exploration and an attempt at
histologic confirmation. References 1.
Gliomas that arise within the optic nerve of children appearto have different features from those found in adolescents and adults.
2.
Matson, D. D.: Neurosurgery of infancy and childhood. Springfield, Ill., Charles C Thomas, 1969,
pp. 523-36. Hoyt, W. F., and Baghdassarian, S. H.: Optic glioma of childhood. Br. J. Ophthalmol. 53: 793, 1969.
3. Zulch, K.
lesions. Pneumoencephalography combined with tomography of the sellar region is the most informative approach for demonstrating intracranial and -chiasmatic gliomas. 2,4
560
J.: Brain pathology, 2nd ed.
lishing Co., 4.
tumors, their
New York,
biology Springer
and Pub-
1965.
W., Love, J. E., Craig, W. M., Dockerty, M. B., Kearns, T. P., Holman, C. B., and Hayles,
Dodge,
H.
A. B.: Gliomas of the
79: 607, 1958.
optic
nerve.
Arch. Neurol.
5.
6. 7.
8.
9.
W. F., Meshel, L. G., Lessell, S., Schatz, N. J., and Suckling, R. D.: Malignant optic glioma of adulthood. Brain 96: 121, 1973. Tym, R.: Piloid gliomas of the anterior optic pathways. Br. J. Surg. 49: 322, 1961. Martin, P., and Cushing, H.: Primary gliomas of the chiasm and optic nerves in their intracranial portion. Arch. Ophthalmol. 52: 209, 1923. Udrarhelyi, G. B., Khodadoust, A. A., and Walsh, F. B.: Gliomas of the optic nerve and chiasm in children. Clin. Neurosurg. 13: 204, 1965. Kier, E. L.: The infantile sella turcica. Am. J. Radiol. 102: 747, 1968.
Hoyt,
In a thought-provoking article,’ Mr. Alan Mushin makes observations of importance to pediatricians. He points out that a level of 40 per cent oxygen in the incubator is not necessarily &dquo;safe&dquo;
for an infant; with normal or nearly normal lung function, 40 per cent may well be toxic. Furthermore, with infants weighing less than 1,500 g, 50 per cent show mild changes of retroleiztal fibroplasia. This suggests that in such infants the vasculature immaturity of the retina is such that retrolental fibroplasia is to be expected almost as part of the price for the short gestation. He points out also that the infant with multiple apneic spells, in whom oxygen monitoring is difficult if not impossible, is a candidate for retrolental fibro-
plasia. an
In my
experience, such as high a risk of
own
infant has
10. Matson, D. D., and Crigler, J. F.: Management of craniopharyngioma in children. J. Neurosurg. 30: 377, 1969. 11. Cushing, H.: The chiasmal syndrome of primary optic atrophy and bitemporal field defects in adults with a normal sella turcica. Arch. Ophthalmol. 3: 505, 1930. 12. Bailey, P., and Herrman, J. D.: The role of the cells of Schwann in the formation of tumors of the peripheral nerves. Am. J. Pathol. 14: 1, 1938. 13. Condon, J. R., and Rose, F. C.: Optic nerve glioma. Br. J. Ophthalmol. 51: 703, 1967.
fibroplasia as the infant respiratory distress syndrome. Many infants with mild retrolental fibroplasia may develop tortuous retinal vessels and myopia. This myopia may have important retrolental
with
consequences for future visual development, especially if it is unilateral (for the disease process may be asymmetric in the two eyes) and goes undetected for it may give rise to anisometropia and aniso-
Retinopathy in Weight Infants
Low Birth
metropic amblyopla.’ References 1. Mushin, A. S.:
Retinopathy of prematurity—a disease of increasing
2.
incidence. Transactions of the Ophthalmological Society of the United Kingdom 94: 251, 1974. Flynn, J. T.: Annotation. In Developmental Medicine and Child Neurology, August 1975.
561
Malignant Gliomas Some
W. H. Brooks, M.D.,*
~~ LIC3~~~S’ acteristically
of
Diagnostic Comments
Joseph
C. Parker, Jr., M.D.,** A. B.
&dquo;the optic pathway char-
in childhood, with a peak incidence between two and six years These gliomas, comprising less than 1 per cent of all aliomaS,3 are frequently not considered in the differential diagnosis of central nervoccur
ous
system
tumors.
these lesions can be divided into distinct groups, each having its own characteristic behavior. Gliomas which originate in that portion of the optic nerve which is in the orbit extend through the optic foramen and characteristically present with proptosis and failing vision. Since they do not give rise to extraocular muscle palsies, they are easily differentiated clinically from the other more malignant tumors of this region which originate from the ocular muscles or the bony orbit. Generally, optic nerve gliomas in this region do riot present a diagnostic problem and furthermore hold
Clinically,
two
*
Assistant Professor, Division of Neurosurgery, UniMedical Center, Lexington, Ky. Associate Professor and Director of Neuropathology, Department of Pathology. t Assistant Professor, Division of Neurosurgery. &Dag er; Assistant Professor, Division of Neurosurgery. Correspondence to W. H. Brooks, M.D., Division of Neurosurgery, University of Kentucky Medical of Kentucky versity **
Center,
Lexington, Ky. 40506.
of the Optic Chiasm in Adolescents Based on Experiences with Two Patients
Young, M.D.,†
R. H. Mortara,
M.D.‡
good prognosis.’ Unfortunately, they acfor only one-third of the gliomas occurring within the optic pathway. The more commonly occurring lesions arise intracranially from the optic chiasm. They have a quite different and varied clinical presentation, which makes their precise diagnosis more challenging. The purpose of this presentation is to illustrate the difficulty in diagnosing these optic pathway gliomas, particularly during adolesa
count
cence
when endocrine abnormalities and features of the tumor are promi-
malignant nent.
Case
Reports
Case 1. A 13-year-old girl had a four-month of visual loss, polydipsia, polyuria, and headache. Measurements showed her to be in the tower 10 percentile range of normal height and weight. No other physical abnormality was evident. Neurologic examination showed optic atrophy with marked limited visual acuity and abnormal peripheral vision (Fig. 1). Blood count, blood chemistry studies, and urinalvses were all normal. Plasma cortisol, PBI, T;¡, T~, TSH, LH, and GH assays indicated panhypopituitarism. Skull films demonstrated suprasellar calcification (Fig. 2). Cerebral angiography depicted no vessel displacement or circulatory alteration. Conray ventriculogram illustrated blunting and
history
557
FIG. 1. Nonspecific defects in the peripheral vision of Cases I and 2 as determined by tangent screen
elevation of the floor of the anterior third ventricle by a suprasellar mass, presumedly a
craniopharyngioma (Fig. 3). Operative exposure revealed a markedly hypertrophied and gray optic chiasm consistent with a malignant glioma. Calcification was noted within the arachnoid covering the chiasm. There was no evidence of tumor extending into the third ventricle or within the sella. A biopsy from the
posterior portion
perimetry.
of the chiasm
scanty tissue and demonstrated
yielded very only lymphoid
cellular infiltrates and fibrous tissue consistent with reactive changes to an adjacent malignant glioma. No neuroglial tissue was seen. Despite 5500 R to the chiasmatic region, the patient’s vision has progressively deteriorated. She is presently blind with severe hypothalamic dysfunction. Case 2. A 20-year-old girl was admitted with
FIG. 2. The suprasellar calcification noted in Case 1 suggested the presence of a craniopharyngioma.
558
FIG. 3. Conray ventriculogram indicating a mass lesion in the region of the optic chiasm-hypothalamus.
history of amenorrhea, weight gain, personality change, polvdipsia, and p«lyul&dquo;ixz. Except for obesity, the physical examination was normal. Neurologic examination showed hilateral optic atrophy, limited vistzal acuity and abnormal peripheral vision (Fig. 1). The usual routine laboratory tests were normal. Plasma cortisols, a
one-year
PBI, T3’ T4, TSH, LH, and GH assay results indicated panhypopituitarism. Skull x-rays sugan enlarged sella. Cerebral angiography normal. Pneumoencephalography illustrated absence of filling of the anterior third ventricle similar to the first patient. The preoperative diagnosis was a craniopharyngioma or a chrazrzaphobe adenoma. At operation, the optic chiasm was hypertrophied. Biopsy yielded scanty tissue which contained malignant astrocytes, prominent and leptomeningeal perivascular lymphoid cellular infiltrates (similar to Case 1), and atypical gemistocytes diagnostic of a moderately differentiated (grade II) astrocytoma (&dquo;astroblastoma&dquo;). The patient has become worse despite radiation therapy and is presently moribund.
gested
was
Discussion These cases clearly demonstrate the difficulties in recognizing an optic chiasm lesion from clinical and radiologic studies. Both presented with endocrinopathic symptoms which suggested a sellar or suprasellar lesion but did not specifically indicate a
chiasmal glioma. Three important features of cases of this type warrant discussion.
Hypothalamic-Pituitary The
occurrence
of
Dysfunction
hypothalamic dysfunc-
is unusual as an initial Such involvement of the presentation.2,4-6 axis hypothalamic-pituitary by chiasmal gliomas was initially observed l~y Martin and Cushin_.7 Reviewing the Mayo Clinic experience, Dodges al.~ noted that only 9 of 46 patients with optic nerve gliomas exhibited endocrine abnormalities. Those that arose intracranially were associated with increased intracranial pressure. The endocrinopathies in their cases appeared late in the disease and were mild .6 When hypothalamic dysfunction develops in adults with malignant chiasmatic gliomas, it is usually late and death is imminent.5 Hypothalamic dysfunction associated with chiasmal gliomas is caused by direct compression and extension of the tumor into the hypothalamic region or through its compromising of the vascular supply. In our cases, since operative inspection indicated no direct tumor extension or infundibular compression, vascular obstruction and the subse-
tion,
as
in
Axis
our cases,
559
quent ischemia was likely responsible the endocrinopathy.
for
Radiologic Findings Routine skull examinations show abnormal findings in about 75 per cent of the patients with gliomas which arise in the orbit and extend through the optic foramen. In contrast, the x-rays are frequently normal in patients with intracranial gliomas arising in the optic chiasm.1,11 The customarily described radiographic findings of the former type of optic gliomas are asymmetrical enlargement of the optic canal and a so-called &dquo;J&dquo; or &dquo;gourd&dquo; shaped sella.1,2,4,6,7,13 Though
strongly suggestive, these findings are not pathognomonic because 20 to 25 per cent of normal individuals have slight asymmetric enlargement of one of the optic foramina. Therefore, only gross asymmetry with or without rounding of the usual rectangularshaped canal should be deemed abnormal. A &dquo;J&dquo; shaped sella is less specific; it may be found in children with various other pathologic conditions’ as well as in some normal infants. The rare and misleading radiographic feature of suprasellar calcification noted on the lateral skull x-rays of Case 1 deserves emphasis. Such calcification in a child sug-
gests
a
craniopharyngioma,1,10 particularly
when in conjunction with hypopituitarism and visual field defects. Cushingil and Bailey&dquo; have described instances of suprasellar calcification within an optic nerve glioma. Since their patients had no endocrine abnormalities, the presence of a craniopharyngioma was not suspected as in our case. Cerebral angiography may help in defining larger tumors and in excluding vascular
Loss of the normal
configuration of the anterior third ventricular recesses, obliteration of the chiasmatic cistern, and outline of the tumor within the interpenduncular cistern can usually be well demonstrated. But when the tumor is confined to the orbit, pneumoencephalography gives normal findings. Pathology Gliomas that arise within the optic nerve of children appear to have different features from those found in adolescents and adults. The &dquo;classical&dquo; childhood optic nerve gliomas usually have limited growth potential and their course resembles that of a hamartoma.~ Malignant degeneration usually does not
develop, so that the prognosis is good even with biopsy or partial resection.’ 2,4,6,8 The gliomas observed in our patients were similar to chiasmatic gliomas appearing in adulthood.5 Histologically, one tumor demonstrated pleomorphic malignant changes suggestive of an aggressive neoplasm. Final Comments From the records of our patients and a survey of the literature, two conclusions can be reached. First, a chiasmatic glioma must be considered in the differential diagnosis of hypothalamic-pituitary axis dysfunction even when suprasellar calcification may be demonstrable. Secondly, gliomas of this region in adolescent patients are not necessarily hamartomatous in nature and should not be considered benign lesions without a surgical exploration and an attempt at
histologic confirmation. References 1.
Gliomas that arise within the optic nerve of children appearto have different features from those found in adolescents and adults.
2.
Matson, D. D.: Neurosurgery of infancy and childhood. Springfield, Ill., Charles C Thomas, 1969,
pp. 523-36. Hoyt, W. F., and Baghdassarian, S. H.: Optic glioma of childhood. Br. J. Ophthalmol. 53: 793, 1969.
3. Zulch, K.
lesions. Pneumoencephalography combined with tomography of the sellar region is the most informative approach for demonstrating intracranial and -chiasmatic gliomas. 2,4
560
J.: Brain pathology, 2nd ed.
lishing Co., 4.
tumors, their
New York,
biology Springer
and Pub-
1965.
W., Love, J. E., Craig, W. M., Dockerty, M. B., Kearns, T. P., Holman, C. B., and Hayles,
Dodge,
H.
A. B.: Gliomas of the
79: 607, 1958.
optic
nerve.
Arch. Neurol.
5.
6. 7.
8.
9.
W. F., Meshel, L. G., Lessell, S., Schatz, N. J., and Suckling, R. D.: Malignant optic glioma of adulthood. Brain 96: 121, 1973. Tym, R.: Piloid gliomas of the anterior optic pathways. Br. J. Surg. 49: 322, 1961. Martin, P., and Cushing, H.: Primary gliomas of the chiasm and optic nerves in their intracranial portion. Arch. Ophthalmol. 52: 209, 1923. Udrarhelyi, G. B., Khodadoust, A. A., and Walsh, F. B.: Gliomas of the optic nerve and chiasm in children. Clin. Neurosurg. 13: 204, 1965. Kier, E. L.: The infantile sella turcica. Am. J. Radiol. 102: 747, 1968.
Hoyt,
In a thought-provoking article,’ Mr. Alan Mushin makes observations of importance to pediatricians. He points out that a level of 40 per cent oxygen in the incubator is not necessarily &dquo;safe&dquo;
for an infant; with normal or nearly normal lung function, 40 per cent may well be toxic. Furthermore, with infants weighing less than 1,500 g, 50 per cent show mild changes of retroleiztal fibroplasia. This suggests that in such infants the vasculature immaturity of the retina is such that retrolental fibroplasia is to be expected almost as part of the price for the short gestation. He points out also that the infant with multiple apneic spells, in whom oxygen monitoring is difficult if not impossible, is a candidate for retrolental fibro-
plasia. an
In my
experience, such as high a risk of
own
infant has
10. Matson, D. D., and Crigler, J. F.: Management of craniopharyngioma in children. J. Neurosurg. 30: 377, 1969. 11. Cushing, H.: The chiasmal syndrome of primary optic atrophy and bitemporal field defects in adults with a normal sella turcica. Arch. Ophthalmol. 3: 505, 1930. 12. Bailey, P., and Herrman, J. D.: The role of the cells of Schwann in the formation of tumors of the peripheral nerves. Am. J. Pathol. 14: 1, 1938. 13. Condon, J. R., and Rose, F. C.: Optic nerve glioma. Br. J. Ophthalmol. 51: 703, 1967.
fibroplasia as the infant respiratory distress syndrome. Many infants with mild retrolental fibroplasia may develop tortuous retinal vessels and myopia. This myopia may have important retrolental
with
consequences for future visual development, especially if it is unilateral (for the disease process may be asymmetric in the two eyes) and goes undetected for it may give rise to anisometropia and aniso-
Retinopathy in Weight Infants
Low Birth
metropic amblyopla.’ References 1. Mushin, A. S.:
Retinopathy of prematurity—a disease of increasing
2.
incidence. Transactions of the Ophthalmological Society of the United Kingdom 94: 251, 1974. Flynn, J. T.: Annotation. In Developmental Medicine and Child Neurology, August 1975.
561
