Residents’ Teaching Giant Jane
j
Cell
A. Lee, Olan,
I
Files Tumor
MD
MD
#{149} William
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0.
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cell
does.
Because
number
tumor
rarely of its
#{149} Manuel
Gonzalez-Melendez,
MD
#{149} Wayne
MD
occurs rarity
differential
plasms
diagnoses
involving
the
that
indistinguishable
granuloma, “brown and are radiographically
cell
tumor.
clinical,
Thus,
whom
true
CASE
the
and
giant
cell
went
tympanotomies
later, left
the
facial
denied
no
with
cornea!
diagnosis
least
of benign are
Benign
when likely
and
malignant
radiographically
tumors
such
it
of a large neo-
or as giant
histo-
cell
re-
and aneurysmal bone cyst contain gidifficult to differentiate from true of giant
cell
In this
article,
bone
He
was
that
tumor
of the
we
verified
skull
describe
with
requires
a patient
such
mobility
in
correlation.
sion
were
normal.
Index
terms:
Giant
cell
tumor,
10.3182
Skull,
#{149}
deafness, had
swelling
tenderness.
One
trismus,
vertigo,
developed
there
with
definite
Although
the
was
a consensual
palsy. The patient’s tongue on the left side. Laboratory
diseases,
loss.
condition.
rapidly.
or infection.
directly,
indicating facial nerve and he had no hearing
of hearing
patient’s
symptoms
facial and
stimulated
new
trauma
left-sided
jaw
complaining the
of left-sided
these
of cranial
disclosed when
physician
to improve
complaining
stated
history
impaired
care
failed
returned
any
reflex
the right side, on protrusion,
10.274,
10.1545,
10.3183,
10.531
left
facial
asym-
eye
exhib-
response
on
deviated to the right test results at admis-
Skull,
#{149}
primary
neoplasms.
10.3221
RadloGraphics ‘From the University
1998;
18:1295-1302
Departments of Radiology Medical Center, 901 23rd
receivedjuly
©RSNA,
patient
examination
along
11)3182.
variety
tumor.
dilemma
is the
of which
cherubism, histologically
to his primary
weakness.
patient Physical
ited
tumor
PRESENTATION
man
metry
a wide
temporal
a diagnostic
cell
correlation.
of the
tube
The
poses
some cell
definitive
Polyethylene month
giant
pathologic
A 20-year-old
and
include
tumors,” and
tumor
but giant
region,
from
radiologic,
skull
location,
craniofacial
logically
giant
in the
in this
parative ant cells
and
MD
Bank,
Tabbara,
SkuiP
INTRODUCTION
Giant
.
of the
1: acceptedJuly
(J.A.L., St, NW, 1. Address
W.O.B., M.G.-M., W.J.O.) Washington, DC 20037. reprint
requests
and Pathology Received May
(SOT.), 8, 1998;
The revision
George Washington requested May
20
toJ.A.L.
1998
1295
1. Frontal radiograph (Waters projection) shows opacification of the inferolateral aspect of the left Figure
maxillary
sinus
posterior
maxillary
sion of the ral fossa.
mass
with
erosion
wall into
of the
and exten-
the
infratempo-
I
2. (a) Axial contrast material-enhanced CT scan shows a heterogeneously the left temporal bone and the lesser wing of the sphenoid bone. The mass extends apex, maxillary sinus, and posterior aspect of the left orbit. (b) Axial CT scan (bone level higher than a shows extensive destruction of the left temporal bone, squamous
enhancing mass involving into the squamous petrous window) obtained one petrous apex, posterior
orbital
mastoid
Figure
wall,
and
lesser
wing
of the
sphenoid
bone.
A series of radiographs of the facial bones was obtained. A frontal radiograph (Waters projection) demonstrated increased density in the left maxillary sinus inferolaterally with no clearly evident bone abnormalities (Fig i). These indeterminate findings prompted cornputed tomography (CT) of the head.
Fluid
or tissue
opacifies
Head mass
#{149}Special
Exhibit
left
CT demonstrated
replacing
cells.
a large
a significant
soft-tissue
portion
of the
tem-
poral bone, with extension intracranially and downward into the infratemporal fossa (Fig 2). The tumor was flattening the posterior aspect of the left maxillary sinus and compressing the left eustachian tube, causing fluid to fill the mastoid
1296
the
cells.
CT
tered
contrast
mass
along
the
orbit
and
findings
with
agent
intravenously
revealed
lateral
orbital
suggestive
adminis-
extension wall
and
of large
Volume
of the into
the
vessels
18
Number
5
Figure
3.
(a) Axial
gadolinium-enhanced
TI-
weighted MR image shows a solid, heterogeneously enhancing mass with multiple flow defects occupying the left infratemporal fossa and bowing the posterior wall of the maxillary sinus anteriorly. The internal carotid artery appears encased. (b) Coronal gadolinium-enhanced Il-weighted MR image of the left in-
fratemporal the
left
fossa
hancement tive
demonstrates
temporal
lobe
of the dura
of dural
MR image
invasion.
shows
elevation
by the
tumor
mater, (c)
en-
findings
Axial
the solid,
of
with
sugges-
12-weighted
heterogeneous
mass in the left infratemporal fossa containing areas of high signal intensity as well as flow voids, which represent different types of tissue. Multiple left mastoid cells are filled with fluid. C.
Cerebral
angiography,
occlusion
within the tumor matrix. 6.0 x 6.0 x 5.0 cm (height and moderately displaced
The
mass
x width
the
measured x depth)
adjacent
struc-
were supply
termine
testing,
performed and
tures.
case
Magnetic resonance (MR) imaging (Fig 3) helped confirm the CT findings of a large heterogeneous mass that enhanced after administration of gadopentetate dimeglumine and en-
ing surgery, to resection.
cased
the
petrosal
and
high
cervical
branches cessory
carotid
tumor
the
drainage
vascular
of the
reserve
occlusion
of the
became
of the
left
middle left
arterial tumor,
de-
brain
in
necessary
and devascularize The tumor was
meningeal,
carotid
embolization
to demonstrate
venous
the
provocative
and
dur-
the tumor prior supplied from meningeal,
anterior
deep
left
ac-
temporal,
segments
of the left internal carotid artery. Osteosarcoma was strongly suspected on the basis of the MR imaging findings.
September-October
1998
Lee
et al
U
RadioGraphics
U
1297
and left posterior auricular arteries (Fig 4). The tumor was embolized through the first three branches with iOO-.tm polyvinyl acetyl foam particles (PVA 100; Cook, Bloomington, Ind). As stasis in the tumor was achieved, the proximal feeding vessels were occluded with fibered microcoils (Target Therapeutics, Fremont, Calif). The rapid arteriovenous shunting
rr
I ,_.
seen in multiple locations prior to embolization was considered unusual for an osteosarcoma and raised the possibility of other aggressive tumors. At surgery, the temporalis muscle was reflected and a large, friable, brown soft-tissue mass
was
seen
eroding
through
the
squamous
portion of the temporal bone. The poorly demarcated tumor appeared to occupy the entire left infratemporal fossa. The external auditory canal and the middle and inner ear had been destroyed. The tumor had avulsed the tympanic membrane and ossicles and eroded through the semicircular canals. The facial nerve required decompression from the styloid foramen to the internal auditory canal. These findings accounted for the patient’s clinical presentation of complete left-sided deafness and left facial nerve palsy. The contents of the infratemporal fossa were resected. The tumor adhered to the dura mater where it extended into the middle cranial fossa. However, microscopic resection revealed an intact dura mater with no evidence of dural invasion at gross examination. The tumor contained multiple large vessels that had been thrombosed by the preoperative embolization and was removed with little blood loss. The internal carotid artery was preserved. The specimen was sent for surgical pathologic analysis an4 was received in several irregular pieces of friable, variegated, focally hemorrhagic and necrotic tissue with aggregate dimensions of 5.0 x 3.0 x 1.0 cm. At histologic analysis, this specimen displayed the classic features of a giant cell tumor. It contained numerous multinucleate cells in a diffuse distribution. The giant cells resembled osteoclasts and contained a large number of centrally lo-
A4
L Figure
4. Lateral subtraction arteriogram obtained with selective injection into the left maxillary artery prior to embolization shows the downward and outward bowing of the maxillary artery and the bowing of the middle meningeal artery. Rapid arteriovenous shunting is seen from branches of the middle meningeal, accessory meningeal, anterior deep temporal, and posterior auricular arteries.
cated,
well-defined
cytoplasm
(Fig
nuclei 5a).
The
in an eosinophilic final
diagnosis
cell tumor was made on the basis ground population of predominantly dral
and
spindle
stromal
of giant
of the backpolyhe-
mononucleate
cells.
The stroma was vascular with areas of hemosiderin-laden macrophages, findings suggestive of hemorrhage. The use of CD68 immunoperoxidase stain confirmed the monocytic and histiocytic origin of the monoand multinucleate giant cells (Fig 5b). Although approximately haLf of all giant cell tumors contain reactive osteoid, predominantly at the advancing edge of the tumor, reactive osteoid was not evident in this case. Several focal islands
of calcified
“chicken
though
wire”
the
chondroid appearance
presence
gests
a diagnosis
droid
matrix
caused
by
matrix were
of chondroid
with
giant
also cell
be identified tumors.
In this
Al-
matrix
of chondroblastoma,
can
a
identified.
sug-
chon-
in fractures case,
the
foci were small and few in number and were considered of no diagnostic significance. The patient underwent craniotomy and debulking of the skull-based tumor, tolerating the procedure without complications.
1298
#{149}Special
Exhibit
Volume
18
Number
5
#{149}#{149}..
.,1Mr-..
Pr
i.....:
Figure
5.
(a) Photomicrograph
polyhedral,
mononucleate
cleate
cells
the
giant
with
background.
(original
cells
numerous
(b)
nuclei
Higher-power
monocytic-histiocytic
origin
magnification, x50; background, characteristic
in the
similar
to those
photomicrograph
of the mono-
tients
with
tumors
giant
and multinucleate
and
cases
of giant
only and
tumors,
four
the
regions
of the
mastoid
process.
cell
1 1 tumors one
each
tumor,
bone
(with
associated
Paget
poral
bone
(2).
giant
craniofacial region with Paget disease is extremely sis
in the
of craniofacial
sphenoid bone,
and
tumor
or without rare and initial
aggressive
tem-
of the
associated may not
differential
be
diagno-
masses.
Giant cell tumor of bone usually with benign histologic features but cally
bone frontal
disease), cell
found
and
even
manifests can be lo-
metastasize.
neoplasms mors,
are 75%-90%
September-October
giant
cell
are found
1998
tumors
in long
(4);
of these
bones
giant
cells.
as the
cells
femur,
tibia,
develop
by
sheets multinu-
are also scattered
stain)
helps
confirm
radius,
and
humerus,
7% involve the spine. velop by endochondral
Giant
cell
ossification.
in
the
and
tumors
intramembranous
of
de-
The
cranial
ossifica-
tion and are therefore cell tumors (5). When occur in the cranium, located in the sphenoid At radiography, giant relatively well-circumscribed, that may cause cortical
an unlikely site for giant true giant cell tumors do they are most commonly bone (2). cell tumor is typically a expansile lesion thinning. About 40% of
giant
cell
a “soap
ance bone
that represents reactive formed by appositional
mors
percent of giant cell tumors are malignant. Benign giant cell tumor has a 3:2 female predilection and usually manifests in the 3rd or 4th decade of life (3). Pain is the most common chief complaint, followed by localized sweffing and tenderness. However, the signs and symptoms associated with this tumor are more closely related to its location than to characteristics of the tumor itself. It is estimated that 3%-7% of primary bone
stain) demonstrates of bone. Large,
in the mononucleate
tumors
is usually
Twenty
tumor
immunoperoxidase
bones
of 2,046
et a! (2)
in the
had
sphenoid
In a review
occipital
A true
of whom
Bertoni
located in the
a consideration
41 1 pa-
cell
involving
bone
evaluated
found (CD68
.
DISCUSSION Dahlin (i) retrospectively
hematoxylin-eosin of giant cell
.#{149}r’
have
located
within
peripherally
the
cranium
and usually manifest Cortical breakthrough sion
is common.
do not tures
possess that
appear-
tend
to be
aggressive
as purely lytic lesions. with soft-tissue extenGiant
any
enable
bubble”
trabeculae of bone growth that (3). Giant cell tu-
cell
unique
definitive
tumors
radiographic diagnosis.
of the
skull
feaBenign
and malignant tumors originating from bone and adjacent soft tissues may appear identical at radiography and must be included in the diiferential diagnosis. In this case, osteosarcoma was
prior
one
of the
foremost
differential
diagnoses
to angiography.
tu-
such
Lee
et a!
#{149}RadioGrapbics
#{149}1299
Histologic nosis
of giant
evaluation cell
is essential
in the
At gross
examina-
tumors.
diag-
initially
sites
of trauma
thought
to arise
or infection
from
and
previous
to represent
a
tion, these tumors are composed of friable, vascular soft tissue whose surface may vary from brown to red, yellow, orange, or gray depending on the degree of necrosis and hemorrhage. Focal areas of collagen deposition and broad bands of hypocellular white fibrous tissue are also seen. Larger lesions usually contain various degrees of necrosis, hemorrhage, and cyst formation (5). Giant cell tumors exhibit a vascularized background network of round, oval, or
reactive inflammatory process. Other theories postulate that the origin of these lesions is periosteal connective tissue, which would explain their increased prevalence in the mandible and maxilla. In contrast, giant cell tumors are thought to represent true neoplasms arising from connective tissue within the bone marrow (8). The actual cause of giant cell reparative granulomas has not been determined. Giant cell reparative granuloma manifests as
spindle-shaped mononucleate cells that do not crowd out the multinucleate cells. These stroma! cells are uniform in size and shape, demonstrate very little atypia, and may engage in mitotic activity. Extensive mitotic activity and atypia may indicate malignant giant cell tumor. Giant cell tumors also contain many homogeneously dispersed multinucleate giant cells composed of abundant eosinophilic granular cytoplasm. Each cell may have from 12 to iOO nuclei, all located centrally (5). These benign tumors exhibit very little osteogenic capability. Osteoid or bone formation may occur but appears to be a reaction to hemorrhage, necrosis, or microfracture rather than the result of metaplasia of the proliferating stromal cells (6). There are a number of cranial lesions that possess multinucleate giant cells and are radiographically and histologically difficult to distinguish from true benign giant cell tumors. These lesions include giant cell reparative granulomas, hyperparathyroidism, cherubism, and aneurysmal bone cysts (7). Radiographic and histologic fmdings alone will not allow defmitive diagnosis of a true giant cell tumor. Giant cell reparative granulomas are not true neoplasms but are extremely difficult to differentiate from giant cell tumors. There are two
a lytic
forms
production
of giant
cell
are pathologically manifestation.
reparative
identical The
peripheral
granuloma
but
differ type
that
in clinical involves
the
gingiva and alveolar mucosa and is rarely associated with bone erosion, whereas the central type involves the mandible, maxilla, ethmoid sinus, sphenoid sinus, and temporal bones (7). Giant cell reparative granulomas tend to affect individuals between iO and 20 years of age and
1300
were
#{149}Special
Exhibit
lesion
that
true giant cell logic analysis, has
cannot
tumor giant
a prominent
be
distinguished
at radiography. cell reparative
fibroblastic
from
At histogranuloma
stroma
that
con-
tains small giant cells arranged in clusters around foci of hemorrhage, creating granuloma-like
arrangements
and
exhibiting
osteoid
formation. Giant cell reparative granulomas contain few nuclei and lack the sheets of giant cells and polygonal mononucleate cells seen in true giant cell tumors (5,7). Giant cell reparative granulomas may recur but never exhibit malignant transformation. In contrast, the recurrence rate of giant cell tumors is estimated at 40%-60%, and malignant transformation occurs in 5%- 1 0% of cases (5). Because the prognosis for patients with giant cell reparative granulomas is vastly different from that for patients with true giant cell tumors,
it is important
diagnosis. ways
Giant
treated
with
cell
tumors
(2).
In this
case
sion,
giant
cell
nated
to make
cell
require
alone,
both
surgery
reparative
cause
as primary,
is a!-
whereas
and
giant
irradiation
a temporal
bone
le-
granuloma
was
elimi-
on the
basis
of histo-
is caused
by
fmdings.
Hyperparathyroidism causes
clinical
granuloma
surgery involving
as a possible
pathologic
a distinct
reparative
of parathyroid
hormone.
of hyperparathyroidism secondary,
are and
tertiary.
increased
The classified The
most
common cause of primary hyperparathyroidism is a parathyroid adenoma. Secondary hyperparathyroidism is a response to chronic hypocalcemia,
most
often
resulting
from
renal
disease or rnalabsorption. Tertiary hyperparathyroidism most commonly occurs in patients undergoing prolonged renal dialysis. Hyperparathyroidism is typically encountered in the 3rd to 5th decades of life. Affected patients present with lethargy, weakness, polydipsia, and poly-
Volume
18
Number
5
uria
that
are
percalcemia,
consequences and
athyroidism
renal
is being
disease
of bone (9).
detected
at an
disease, Hyperparearlier
hystage
than in the past; as a result, only 10%-15% of patients with primary hyperparathyroidism experience skeletal changes (10). Excessive amounts of parathyroid hormone initiate fibroblastic proliferation and increase osteoblastic and osteoclastic activity; this in turn results in softening and deformity of the bone (9). Patients with skeletal abnormalities due to hyperparathyroidism may present with diffuse or focal skeletal changes. Diffuse skeleta! changes are characterized by demineralization followed by increased osteoclastic activity with marked bone resorption and, eventually, marrow fibrosis. This process is known as osteitis fibrosa cystica (10). Focal bone lesions (brown
tumors)
are
characteristic
of primary
hyperparathyroidism and typically involve the facial bones. These lesions are nonneoplastic and actually represent focal accumulations of fibrous tissue and multinucleate giant cells. At radiography, brown tumors appear as lytic lesions that may expand the bone or fracture the cortex. A generalized demineralization or “ground glass” appearance and endosteal scalloping are seen in diffuse skeletal changes (9). At histologic analysis, fibroblastic stroma with clusters of giant cells and foci of hemorrhage create a granulornatous lesion. Interspersed are foci of osteoid and new bone formation. These granulomatous lesions most likely form in response to microfractures. Brown tumor may appear radiographically and histologically similar to giant cell reparative granuloma, and differentiation may be impossible if the clinical findings are not available. In this case, the patient demonstrated no evidence of metabolic abnormalities. The levels of calcium, phosphorus, and alkaline phosphatase were within normal limits, and brown tumor was excluded from the differential diagnosis of the infratemporal mass. Cherubism, or familial fibrous dysplasia, is an autosomal dominant trait that occurs in childhood and is characterized by symmetric involvement of the mandible and the maxilla. Affected
individuals
have
marked
bilateral
jaw
fullness and a slight upward turning of the eyes that gives them a “cherubic” appearance. At histopathologic analysis, these lesions contain giant cells that vary in number and in the amount of fibrous tissue and hemorrhage
September-October
1998
present. At radiography, they appear as a bilateral expansile, multiloculated, cystic mass. These radiolucent lesions may perforate the cortex and cause problems with dentition. Curettage is the treatment of choice. In our case,
the
the
unilateral
lack
this
location
of family
diagnosis
lesion
bone
bone
lesion
cyst
is an
containing
(blow-
blood-
cystic
cavities.
occur
in patients
under
20
bone
most
commonly
Aneurysmal
Ninety
expansile
sions
cysts
metaphysis
may
also
bone
be
seen
and
percent
of long
even
le-
of age. occur
although
diaphysis
such
the
of these years
bones,
in the
or in flat bones
pelvis,
made
thin-walled,
filled
in the
and
for cherubism
unlikely.
Aneurysmal
out)
of the
history
they
of a long
as the
vertebrae.
scapulae,
the
At radiography,
these tumors usually appear as expansile, radiolucent lesions. Aneurysmal bone cysts are an uncommon finding in the paranasal sinus region. Aneurysmal bone cysts can develop de novo or
as a result
lesions
ma,
of cystic
such
giant
changes
in preexisting
as chondroblastoma,
cell
tumor,
osteoblasto-
or fibrous
dysplasia.
At
pathologic analysis, the lesion consists of multiple blood-filled sinusoid spaces alternating with more solid areas. The solid component contains
fibrous
elements
and
numerous
multi-
nucleate giant cells and exhibits rich vascularity. Treatment consists of preoperative embolization and surgical resection. In our case, the pathologic fmdings were not consistent with this
diagnosis.
Malignant niofacial most
and
common
most
of long
ma!
the disease,
occur
malignant as the
percent facial
distal
between
rarely
seen
contrast,
bones,
the
average
femur
with and
10 and
osteosarcoma
tumor
metaphysis or
proxi-
of all osteosarcomas
trauma,
in persons
cra-
second
bone
in the
factors
irradiation
to their development. the long bones occurs
viduals
in the
is the
occurs
such
Eight
from
posing fecting
primary
bones
as Paget
can
Osteosarcoma
frequently
tibia.
arise
mal
neoplasms bones.
age
predis-
Osteosarcoma afprimarily in indi-
25 years
over
such
of age
30 years of patients
and
is
of age.
In
with
cra-
is 30 years.
The radiographic appearance of osteosarcoma varies depending on the amount of osteoblastic and osteolytic activity: Osteoblastic
Lee
et al
U
RadioGraphics
U
1301
lesions appear sclerotic, whereas osteolytic lesions are radiolucent (i 1). Although osteosarcomas commonly manifest with profuse sclerosis, spicular margins, and matrix calcification, they occasionally appear as lytic soft-tissue masses that are radiographically indistinguishable from giant cell tumors. Osteosarcoma is characterized
by
rapid
cludes surgery with chemotherapy tion therapy. The 5-year survival (1 1). In our case, osteosarcoma
and radiarate is 9% was strongly
suspected given the patient’s age and the rapid progression and radiographic appearance of the tumor. However, osteosarcoma was excluded on the basis of biopsy fmdings: The specimen did not contain the increased osteoid ate
cells
pleomorphic
typical
REFERENCES 1 . Dahlin DC. Giant 2.
3.
growth.
At histologic analysis, osteosarcomas may be osteoblastic, chondroblastic, or fibroblastic, depending on cell predominance. However, all types exhibit a malignant spindle cell stroma with interspersed foci of osteoid or bone formation. Treatment for osteosarcoma of the skull in-
formation,
S
stroma,
or
4.
5.
7.
8.
multinucle-
of osteosarcoma. 9.
U CONCLUSIONS Radiology plays a vital role in the diagnosis and preoperative devascularization of giant cell tumors. Clinical, radiologic, and histopathologic fmdings must be considered together to differentiate this lesion from other aggressive tumors and reach an accurate fmal diagnosis.
of skeletal Williams & Henderson of the skull: 23:120-122. Resnick D, like lesions
specific
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RS, Kumar
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ral bone.
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ed. Philadelphia, 10.
cell tumor
lights of 407 cases. AJR 1985; 144:955-960. Bertoni F, Unni KK, Beabout JW, Ebersold MJ. Giant cell tumor of the skull. Cancer 1992; 70:1124-1132. Yochum T, Rowe L. Tumor and tumorlike processes. In: Yochum T, Rowe L, eds. Essentials
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Panda
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