Download half of 1 per cent of intracranial neoplasms.4 In the cas

T H E AMERICAN JOURNAL OF CLINICAL PATHOLOGY
Vol. 45, No. 6
Copyright © 1S66 by The Willinms & Wilkins Co.
Printed in
U.S.A.
GANGLIOGLIOMA OF THE BRAIN STEM
J. C. RICHMOND, M.D., D. L. CUNNINGHAM, M.D., F. G. FUSTE, M.D., AND
CYRUS C. ERICKSON, M.D.
Departments of Pathology and Neurology, University of Tennessee, Memphis, Tennessee
Gangliogliomas comprise less than onehalf of 1 per cent of intracranial neoplasms.4
In the cases reported, there has been a predilection for the floor of the third ventricle
and for the temporal lobes as sites of origin.
Only very rarely has the brain stem been
involved.
It is the purpose of this discussion to
describe a ganglioglioma arising from the
pons region.
R E P O R T OF CASE
B. G., a 4-year-old Negro boy who had
been well prior to the onset of his present
illness, was brought to the admitting ward
with a history of having awakened, 1 hr.
prior to admission, crying out with pain in
the back of his neck. The patient then
vomited once and became limp. He was
not responsive to verbal stimuli from his
parents. No convulsive movements were
noted. Past history revealed that the child
had accidentally fallen, 2 weeks prior to
admission, striking the occipital region of
his head, but had not been rendered unconscious; however, he complained of headaches after the fall.
The child vomited once in the admitting
ward.
Examination revealed blood pressure of
120/70, pulse 60, respirations 28, temperature 97.2 F. General physical examination
was not remarkable. Neurologic examination revealed a patient who responded to
loud noises by opening his eyes. The pupils
were dilated and reacted only slightly to
light. On deep pain stimulation, the patient
moved his right extremities, but not his
left ones. Cranial nerve testing revealed a
weakness of the right peripheral facial nerve
and an absence of the right corneal reflex.
Deep tendon reflexes were increased on the
right and bilateral Babinski signs were
present.
Received, December 2, 19G5.
692
Lumbar puncture was performed at the
time of admission and revealed an opening
pressure of 190 mm. of water with grossly
bloody spinal fluid. Three hours after admission, the temperature rose to 103 F. The
patient was taken to surgery and occipital
burr holes were attempted, but he died on
the operating table before ventriculography
or definitive surgery could be carried out.
Pathologic findings. Gross autopsy findings
revealed: (1) a 5- to 6-cm. soft, gray, tumor
mass arising from the right cerebellopontine
angle, appearing to arise from (he pons;
(2) a diffuse subarachnoid hemorrhage
around the base and right cerebellopontine
angle; (3) massive cerebral edema (weight
1350 Gm.); and (4) cerebellar tonsil herniation with medial approximation.
A midsagittal section of the brain revealed the tumor to arise from the region of
the pons, but to be rather sharply delineated
from the compressed, relatively normalappearing tissue of the pons. A small central
area of necrosis and hemorrhage was noted
(Fig. 1). A definite origin of the subarachnoid
hemorrhage could not be determined.
Microscopic pathologic findings. Microscopically, invasion of normal tissue could
be seen, even though the cellular tumor
was well defined and outlined grossly (Fig.
2).
The tumor was predominantly composed
of fibrillary astrocytes and numerous abnormal neurons scattered diffusely throughout (Fig. 3), with no significant variation
in distribution of the neurons and astrocytes
from central to peripheral zones. Abnormal
and bizarre neurons, varying greatly in size
and shape from large giant cells to quite
small cells, were seen. Many were normal
in size and were well differentiated. Some
were irregularly oriented and exhibited
anomalous "tail-like" processes (Fig. 4).
Binucleate forms could be seen (Fig. 3).
Nissl substance and well-formed nucleoli
June 1966
093
GANCU0GL10MA
FIG. 1. Midsaggital .section of bruin-cleaving tumor mass arising from the right side of the pons. Note
compression of brain-stem tissue and floor of fourth ventricle. Hemorrhage into the leptomeninges at
the level of the interpeduncular fossa and center of the tumor may be seen.
were present. Clumping and grouping of the
chromatin were seen.
Evidence of marked astrocytic proliferation with pleomorphic fibrillary structures
and hyperchromatism was seen (Fig. 4).
A typical pronounced gliomatous infiltrate, with some of the cells being pyknotic
and others, containing several nucleoli and
Nissl substance, being swollen, is shown in
Figure 4.
Minimal spongiosis and rarefaction of the
tumor parenchyma were seen to yield a
delicate glial fiber latticework (Fig. 5), upon
which tumor cells were attached, in association with the anomalous "tail-like" structures and processes of the neurons and neuron-like cells (Fig. 4). Dark, round, satellite
oligodendroglia cells occasionally circumscribed a degenerating neuron (Fig. 4).
Grossly and on low power microscopically,
the tumor appeared to be encapsulated, but
on higher power, tumor cells were seen to
blend into the adjacent brain substance,
which was compressed, giving the tumor its
pseudoencapsulation (Fig. 2).
DISCUSSION
Ewing first suggested the name ganglioglioma because it indicated the 2 essential
constituents of the neoplasm, i.e., ganglion
and glial cells. Gangliogliomas occur most
frequently in children and young adults,
i.e., 60 per cent appear in persons under 30
years of age; however, some gangliogliomas
have been seen in the fifth decade of life.
The growth of the tumor is slow in most
instances and prognosis is good if enucleation
is possible.6 The duration may occasionally
be short; however, in most instances it is
prolonged. The symptoms may last as long
as 20 years. Over the past 30 to 35 years,
there has been controversy in the literature
pertaining to tumors of gangiion-glial origin.
Thus, there have arisen numerous synonyms,
and there has been speculation as to whether
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F I G . 2 (upper). Tumor mass in lower, and compressed brain stem tissue in upper portion of photograph. Hematoxylin and eosin. Reduced 15 per cent from X 00.
F I G . 3 (lower). Section of tumor, showing both cellular components, astrocytes, and neurons. Note
the abnormal binucleate neuron. Hematoxylin and eosin. Reduced 15 per cent from X 200.
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F I G . 4 (upper). Note the large, bizarre, tailed neuron in the lower left corner and the large nucleolus.
The neuron in the upper right corner shows clumping and disarrangement of chromatin and hyperchromatism. Several glial cells may also be seen. Hematoxylin and eosin. Reduced 15 per cent from
X 475.
F I G . 5 (lower). Cajal gold impregnation, showing both cellular components of the tumor, fibrillary
astrocytes, and neurons. Glial fibers are obviously a b u n d a n t . Reduced 15 per cent from X 475.
G95
696
RICHMOND ET
such tumors really exist, or are merely gliomas with inclusions of neurons.
Kernohan and associates5 proposed the
names of neuroblastoma and gangliocytoma,
depending on the maturity of the ganglion
cells. The classification based on predominant cell type was proposed by Wolf and
Morton, 7 as follows: comparatively pure
ganglion cell tumors are to be called ganglioneuroblastoma and gangliocytomas, depending upon the maturity of cells; and
mixed ganglion and glial tumors are to be
called gangliogliomas and ganglioblastomas.
Some of the difficulties which have produced disputes are: a lack of concrete evidence that the ganglion cells actually participate in the tumor and are not just engulfed by the glial astrocytic processes;
an identification of neuroblasts or neuron
cell precursors, in relation to which Bailey
and Beiser1 state that it is difficult, if not
impossible, to identify neuroblasts positively, even with Nissl stains; positive proof
that the cells assumed to be neurons actually
are so, which can be partly resolved with a
special stain technic; the possibility of
malignancy, regarding which Russell and
Rubinstein 6 stated that malignant changes
are restricted to the glial elements, suggesting that, where changes appear to involve
other elements, the tumor probably belongs
to a group called pseudoganglionic giantcell gliomas; and the question whether 1
element (glial cells) first assumes neoplastic
activity and then stimulates the associated
nerve cells to a similar proliferation, or
whether both begin neoplastic development
at the same time, as proposed by Courville.2
Courville and Anderson3 stated that "It
is generally agreed that both nerve (or
ganglion) cells and glial cells play a part in
the elaboration of the tumor. It is, therefore,
a mixed tumor with two distinct cellular
elements contributing to its enlargement."
We believe that this tumor, as illustrated,
is grossly and microscopically typical of the
combined or mixed tumor components of
both nerve (or ganglion) and glial cells which
are described in the literature as ganglioglioma.
Microscopically, we have shown cells of
definite neural origin which exhibit evidence
Vol. 45
AL.
of proliferation and other characteristics of
neoplasia, such as binucleate forms and
pleomorphism. In our opinion, numerous
neurons (or ganglion cells) located 4 to 5
cm. outside the brain stem and associated
with a mass containing bizarre glial cells
cannot be interpreted as normal. No attempt was made to identify neuroblast or
neuron cell precursors. We do not believe
that available methods and material make
it possible to determine which atypical type
cell began proliferation first or whether one
stimulates the other to proliferate.
SUMMARY
The case of a brain stem tumor consistent
with previous descriptions of true ganglioglioma, and occurring in a 4-year-old boy, is
presented.
Ganglioglioma is an uncommon tumor,
and its occurrence in the brain stem is indeed rare.
With gross and microscopic photographs,
we have shown its origin from the area of
the pons.
The tumor possesses neurons which vary
in size, shape, and maturity, and which are
disoriented, abnormally located (out of context), and associated with a Grade II astrocytic proliferation.
REFERENCES
1. Bailey, P . , and Beiser, H . : Concerning gangliogliomas of the brain. J . N e u r o p a t h . &
Exper. Neurol., 6: 24-34, 1947.
2. Courville, C. B . : Multinucleation of cortical
nerve cells a t margin of malignant glioma.
J . Neuropath. & Exper. Neurol., 15: 369-370,
1956.
3. Courville, C. B . , and Anderson, F . M.: N e u r o gliogenic tumors of the central nervous system. Bull. Los Angeles Neurol. S o c , 6:
154-176, 1941.
4. Grinker, R., Buoy, P . , and Sahs, A.: Gangliogliomas or ganglioneuroma. In: Neurology,
Ed. 5. Springfield, 111.: Charles C Thomas,
Publisher, 1960, p. 671.
5. Kernohan, J. W., Learmonth, J. R., and Doyle,
J. B.: Neuroblastomas and gangliocytomas of
the central nervous svsteni. Brain, 55: 287310, 1932.
6. Russell, D . S., and Rubinstein, L. J . : Pathology
of Tumors of the Nervous System, E d . 2.
Baltimore: T h e Williams & Wilkins Co.,
1963, pp. 162-172.
7. Wolf, A., and Morton, B . F . : Ganglion cell
tumors of the central nervous system. New
York Neurol. Inst. Bull., 6: 453^488, 1937.