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Pathologic Quiz Case

Janine C. Malone, MD; Kelly Z. Brown, MD; Joseph C. Parker, Jr, MD; Louisville, KY

he patient was a 46-year-old white man with a history

of hypertension for 15 years (most recently treated
with lisinopril), peptic ulcer disease, arthritis, chronic obstructive pulmonary disease, and hepatitis A 4 years before presentation. He also had a 3-pack-per-day smoking
history for the past 30 years (having quit 1 year before
presentation) and a history of 6 to 8 beers per day for the
past 30 years. Twenty years ago, he had been diagnosed
with and treated for pulmonary tuberculosis.
Radiologic studies included computed tomographic
scan of the head, which demonstrated an inhomogeneous,
calcified left frontal lobe mass crossing the corpus callosum and producing a shift of midline structures. Subsequent magnetic resonance imaging demonstrated a 9 3 6cm, irregular, rim-enhancing left frontal lobe mass with
low signal intensity corresponding to calcification and
several unenhancing areas suggestive of necrosis. Shift of
midline structures and subfalcine herniation were also
noted (Figure 1).
The patient presented with his family, who described
recurrent sudden blackouts in the patient during the
previous 2 weeks. Physical examination revealed a slightly
depressed and lethargic obese man with a blood pressure
of 152/98 mm Hg and a pulse of 85 beats per minute. He
was disoriented to place and time and demonstrated slight
pronator drift of the right upper extremity. Following imaging studies, the patient underwent left fronto-temporo-

358 Arch Pathol Lab MedVol 123, April 1999

parietal craniotomy with near-complete tumor resection.

Following surgery, he received 65 Gy of external beam
radiation. Approximately 3 months after surgery, his family reported increased confusion and right-sided weakness. A repeat computed tomographic scan revealed a
large recurrent tumor mass. The patient died a few weeks
later, nearly 4 months after his initial presentation. Permission for autopsy was denied.
At the time of surgical resection, a large left frontal neoplasm with dural attachment was noted. The meningeal surface was ossified. Pathologic evaluation revealed 190 g of
fragmented, tan to pale yellow, soft to rubbery tissue with
associated white chondroosseous portions. Gross hemorrhage and necrosis were absent. Microscopically, the tumor
demonstrated several patterns. Most prominent were highly
cellular areas composed of malignant spindle cells with a
storiform pattern (Figure 2). These areas demonstrated positive immunoreactivity for CD68 and negative immunoreactivity for glial fibrillary acidic protein. Separate distinct areas of malignant, focally necrotic cartilage and malignant
osseous tissue were also identified (Figure 3). These components exhibited increased mitotic activity with 2 to 5 mitoses per high-power field. Atypical to frankly malignant
astrocytes were present (Figure 4) and demonstrated positive
staining for glial fibrillary acidic protein. Bizarre mitotic figures were occasionally seen (Figure 4, arrow).
What is your diagnosis?

Pathologic Quiz CaseMalone et al

Arch Pathol Lab MedVol 123, April 1999

Pathologic Quiz CaseMalone et al 359

Pathologic Diagnosis
Gliosarcoma Containing Malignant Fibrohistiocytic,
Osseous, and Chondroid Elements
Gliosarcoma is a biphasic neoplasm that contains both
malignant glial and mesenchymal elements. In most lesions, the malignant glial component is glioblastoma multiforme (GBM), although an oligodendroglial component
has occasionally been described. These tumors are rare,
representing between 1.8% and 8% of malignant glial neoplasms.1,2
Feigin and Gross3 described 3 patients with tumors
composed of mixed glial and sarcomatous elements. These
authors postulated that the sarcomatous component arose
from neoplastic transformation of vascular endothelium
within a primary GBM. Many studies utilizing immunohistochemical and ultrastructural markers for vascular origin have both supported and refuted this hypothesis.
Still, these tumors are often referred to as Feigin tumors.
Later investigators classified mixed glial and sarcomatous
neoplasms according to their presumed primary component. In 1979, Lalitha and Rubinstein4 suggested the term
sarcoglioma for malignant mesenchymal brain tumors containing secondary glial elements. They described lesions with a central meningioma or sarcoma surrounded
by gliomatous elements ranging from reactive astrocytosis
to GBM. Based on the tumor arrangement, the authors
proposed that the sarcoma induced the development of
glioma.
A temporal location is classically reported for gliosarcomas, and compiled data support this observation (Table). As in most gliomas, gliosarcomas are more common
in males than females. The majority occur in the aged, as
is the case for most high-grade glial neoplasms. In contrast, sarcogliomas tend to occur in children or young
adults. Gliosarcomas have shown a predilection to arise
in patients having undergone previous cerebral radiation
therapy. The mean survival of patients with gliosarcoma
is similar to that of patients with GBM, being less than 12
months. In contrast to GBM, there is a propensity for
gliosarcoma to disseminate and produce extracranial metastases.6
Neuroimaging reveals a hypodense enhancing mass
that is superficially located within the cerebral parenchyma and often associated with the leptomeninges and dura.
Peritumoral edema is common, and calcification and cystification are sometimes evident. Grossly, gliosarcomas appear firm, discrete, and lobulated. Frequently, there is
meningeal attachment, and the macroscopic appearance
may suggest meningioma. The cut surface is often variegated with firm gritty areas alternating with softened yellow areas. Microscopically, the tumor possesses fascicles
of sarcoma interspersed with GBM in a marbled arrangement. In advanced lesions, neoplastic glial cells may be
only sparsely distributed within the sarcoma. The spindle
cells of sarcomatous areas typically have cytologic features
of malignancy, including pleomorphic nuclei with vesicular or clumped chromatin and prominent nucleoli. Mitotic figures are present, although they may not be abundant. Although fibrosarcoma is the most frequently reported stromal malignancy,7 other patterns resembling
malignant fibrous histiocytoma, rhabdomyosarcoma, os-

360 Arch Pathol Lab MedVol 123, April 1999

Clinicopathologic Data Compiled From 63 Cases of

Gliosarcoma(1,2,5)
Number

Percent

Age,
,40
8
13
4059
27
43
.60
28
44
Sex
Male
35
56
Female
28
44
Location*
Frontal
18
21
Temporal
30
36
Parietal
26
31
Occipital
7
8
Other
3
4
* Tumors located in overlapping lobes are scored in all areas which
apply.

teosarcoma, and chondrosarcoma have been described.5

Special stains help delineate the biphasic nature of these
tumors. Silver stains demonstrate the reticulin-rich stroma
of the sarcomatous component, while glial fibrillary acidic
protein immunoperoxidase techniques decorate the glial
component. Reactivity for histiocytic markers and myoid
markers may be seen in the mesenchymal component of
gliosarcomas.
An area of debate centers on the cell of origin of the
sarcomatous component of gliosarcoma. Ultrastructural
and immunohistochemical studies have suggested a possible endothelial cell origin, as Feigin and Gross3 suggested, whereas other studies have refuted these results. Also
implicated as the cell of origin are adventitial and meningeal fibroblasts, histiocytes, vascular smooth muscle
cells, or some undifferentiated pluripotential mesenchymal cell.
In summary, this case illustrates an unusual malignant
glioma with characteristic gross and microscopic features.
Gliosarcoma should be included in the differential diagnosis of any discrete, superficially located or meningealbased tumor that radiographically or grossly suggests a
meningioma. The diagnosis moves to the forefront if the
tumor arises in the temporal lobe or demonstrates necrosis. The biphasic nature of the tumor may be difficult to
discern if there is a paucity of glial elements or if glial
cells assume a spindled configuration. Reticulin and glial
fibrillary acidic protein stains are helpful in these cases.
References
1. Morantz RA, Feigin I, Ransohoff J. Clinical and pathological study of 24
cases of gliosarcoma. J Neurosurg. 1976;45:398408.
2. Meis JM, Martz KL, Nelson JS. Mixed glioblastoma multiforme and sarcoma:
a clinicopathologic study of 26 radiation therapy oncology group cases. Cancer.
1991;67:23422349.
3. Feigin I, Gross SW. Sarcoma arising in glioblastoma of the brain. Am J
Pathol. 1954;31:633649.
4. Lalitha VS, Rubinstein LJ. Reactive glioma in intracranial sarcoma: a form
of mixed sarcoma and glioma (sarcoglioma), report of eight cases. Cancer.
1979;43:246257.
5. Sreenan JJ, Prayson RA. Gliosarcoma, a study of 13 tumors, including p53
and CD34 immunohistochemistry. Arch Pathol Lab Med. 1997;121:129133.
6. Cerame MA, Guthikonda M, Kohli CM. Extraneural metastases in gliosarcoma: a case report and review of the literature. Neurosurgery. 1985;17:413
418.
7. Burger PC, Scheithauer BW. Tumors of the Central Nervous System. Washington, DC: Armed Forces Institute of Pathology; 1994. Atlas of Tumor Pathology ;
3rd series, No. 10.

Pathologic Quiz CaseMalone et al