Bone and Soft Tissue Pathology
Case 2 -
Osteosarcoma Arising in a Background of Fibrous Dysplasia Of the Sphenoid Bone, Pterygoids and Extending into the Right Nasal Cavity.
Gene P. Siegal
Professor of Pathology
Cell Biology and Surgery
University of Alabama at Birmingham
Click on each slide thumbnail image for an enlarged view
A 55 year old Caucasian woman presented with headache and neck pain of three months duration. She was
otherwise in excellent health without known major illnesses or surgeries. A course of antibiotic therapy
did not relieve her pain. A subsequent trial of steroids was similarly unsuccessful in alleviating her
Three weeks prior to admission she developed blurred vision and "double vision" with drooping of her
left eyelid. On physical examination she appeared healthy but with ptosis of her left eyelid with
inhibition of both lateral and medial gaze. An MRI examination was performed which revealed a 4 cm mass
replacing the sphenoid sinus and extending into the nasal pharynx while compressing and laterally
displacing both internal carotid arteries. The upper tumor margin was seen to be at the level of the
optic chiasm. On a T1 weighted image the signal intensity was isointense to muscle but heterogenous.
The heterogeneity was slightly increased in its intensity on FLAIR and T2 weighted views.
Following intravenous contrast, the lesion demonstrated homogenous enhancement. Replacement of the
cavernous sinuses was noted and the lesion was seen to be slightly larger on the left at the upper margin
and eccentrically expanded to the right-inferiorly. The left wing of the sphenoid was enhanced as was
the tuberculum sella. The brain parenchyma was viewed as normal throughout.
On maxillofacial CT of the sinuses diffuse changes were seen in the skull bones. A large soft tissue
mass was again appreciated involving the sphenoid bone, including its body, greater and lesser wings, and
pterygoids and the lesion was also seen to extend into the right nasal cavity. Marked hyperostosis of
the posterior ethmoid sinus, mainly on the right, with a mass-effect on the posterior aspect of the nasal
septum (causing deviation to the left) was further appreciated. Taken together the changes were thought
to favor the diagnosis of a meningioma radiologically within the sphenoid sinus and pitutitary fossa.
Nasal endoscopy demonstrated a bulging of the posterior nasal cavity inferior to the sphenoid sinus
and superior to the nasopharynx. This mass was smooth and mucosally covered with a thin shell of bone
over the neoplasm. The tumor was white, and fleshy with minimal vascularity. Following endoscopic
evaluation she underwent a biopsy of the mass.
Case 2 - Figure 1 - MRI following contrast demonstrating homogenous enhancement of a mass.
Case 2 - Figure 2 - Maxillofacial CT demonstrating marked changes in the bones surrounding the mass.
Case 2 - Figure 3 - Low power photomicrograph - note tumor osteoid admixed with highly vascular neoplastic spindle cell population & woven bone.
Case 2 - Figure 4 - Higher power photomicrograph - increased mitotic activity is seen.
Multiple sections demonstrated a spindle cell neoplasm with osteoid formation. In some fields
significant cellular pleomorphism and increased mitotic activity (1-3/HPF) were noted within the spindle
cell stroma. Other fields contain woven bone without osteoblastic rimming in the fibrous stromal
Immunophenotypically, the spindle cell population was reactive only with antibodies directed against
vimentin intermediate filaments. Specifically, no reactivity was noted with broad spectrum cytokeratin,
EMA, or S-100 protein antibodies.
Fresh tissue was also collected. After gentle disaggregation and Ficoll separation, 2.2 million cells
were retrieved with low viability. On a Wright stained cytospin, spindled cells and other non-specific
stromal elements identical to that found in the tissue were identified. Thus, flow cytometry was not
The patient was offered pre-operative cisplatin, adriamycin and methrotexate based chemotherapy
regimen followed by surgery to debulk the tumor. It was anticipated that she would complete her therapy
with post-surgical gamma knife irradiation.
She received three courses of chemotherapy which except for modest marrow suppression was well
tolerated. The patient regained function of her left eye and felt clinically significantly improved.
She refused further pre-operative therapy and went to a private practitioner in the Midwest for radical
resection of the tumor mass. She then sought post-operative care at an eastern academic institution.
She died, presumably of her disease or its sequella, approximately nine months following her initial
Osteosarcoma arising in a background of fibrous dysplasia of the sphenoid bone and pterygoids and
extending into the right nasal cavity.
Introduction to the Discussion
Fibrous dysplasia (FD) is a proliferative process involving primarily the intramedullary portion of
from one to many bones. It is composed of randomly distributed spicules of woven bone, absent prominent
osteoblastic rimming, set in a background of swirling fibrous connective tissue with occasional focal
cartilaginous differentiation. FD occurs in children and adults on every populated continent and does
not favor or spare any racial or ethnic group. Although the monostotic from in some studies slightly
favors women, it is considered equally prevalent in both sexes.
Select sites of involvement appear to favor one gender over the other, e.g., long bones more often
involve women whereas ribs and the skull are favored sites in men
. In the monostotic form, about 35% of cases involve the head, a second 1/3 occur in the
femur and tibia, and an additional 20% in the ribs. Whereas, in the polyostotic form, the femur, pelvis,
and tibia are involved in the majority of cases . The
gnathic bones appear to be over represented  while the
spine is a relatively rare site of involvement .
FD may present in a monostotic or polyostotic form, and in the latter case, can be confined to one
extremity or one side of the body or be diffuse. The polyostotic form is six times less frequent than
the monostotic form  and it is usually first discovered in
late childhood. The polyostotic form often manifest earlier in life than the monostotic form
. The lesion is often asymptomatic but pain and fractures
may be part of the clinical spectrum . FD may also be
associated with oncogenic osteomalacia . FD is linked to
many genetic disease and morphologic conditions. Examples of this include: mucoceles
, simple or empty cysts  and
aneurysmal bone cysts . The polyostotic form of FD is
intimately associated with McCune-Albright syndrome. There is a relationship between polyostotic FD and
intramuscular myxomas (Mazabraud's syndrome) .
Patients are at increased risk for malignant transformation, even greater than those with FD alone
(thought to be <0.5%) . The presence of FD plus
osteosarcoma is the most common form of malignant transformation
. Other malignant tumors associated with FD include chondrosarcoma
, fibrousarcoma ,
angiosarcoma and MFH .
Radiologic imaging of FD can be divided in three broad types: sclerotic, osteolytic, and mixed
patterns . FD is often said to have pathognomonic
radiologic characteristics , which include a ground
glass texture and sclerotic rim. Classically, FD shows cortical thinning and bony expansion with
occasional full thickness bony destruction mimicking aggressive tumors
. The value and limitations of computerized tomography in FD has been reported
. Its greatest strength lies in its ability to
demonstrate the amorphous ground glass appearance of the lesion and its ability to define the extent of
the disease . MR better defines FD via sharply defined
borders with intermediate signal intensity on T-1 and with T-2 weighted images demonstrating a pattern of
either high or intermediate to low intensity . On
scintigraphy, FD lesions have slightly increased perfusion and markedly increased uptake of tracer
The fibrous areas contain an overabundance of pre-osteogenic cells while the lesional bone is
responsible for the biosynthetic output of mature but abnormal osteoblasts
. Clonal structural chromosomal aberrations have been noted in
chromosomes 3, 8, 10, 12, and 15 . In a manuscript by
Dal Cin and colleagues clonal chromosome aberrations were reported in 8 out of 11 cases of FD, suggesting
that this entity is neoplastic in nature. The only recurrent changes have been structural rearrangements
involving 12p13 and trisomy 2 . An activating missense
mutation in the gene encoding for the alpha subunit of heterotrimeric signal transducer of G protein that
stimulates cAMP formation apears to be responsible for FD associated with McCune-Albright Syndrome and
probably all other forms as well .
Gross: The bone is often markedly distorted with a firm-to-gritty consistency. Its color
varies from and it is often filled with multiple cysts, containing yellow-tinged fluid
. When cartilage is present, it often stands out as sharply
circumscribed of blue-tinged translucent material  .
Histomorphology: The histopathology is that a bizarre C-shaped metaplatic bone devoid of
rimming osteoblasts. This atypical woven bone often contains central mineralization and while grossly
appearing to be relatively well circumscribed,invades the surroiunding bone. Osteoclasts may be present
singularly or in clusters . The fibroblastic spindle
cell population dominates in most cases of FD. The density of the fibrous component varies greatly even
within the same lesion and cartilage differentiation is not usual
Immunophenotype: Immunohistochemistry has not afforded significant advantage for diagnosis or
prognosis. The fibrous component is immunoreactive with antibodies directed against vimentin and with
XIIIa . The bone spicules are "positive" with
antibodies directed at osteonectin . The lesion is
also immunoreactive for prostaglandin E-2, estrogen receptor as well as progesterone receptor
. FD is immunoreactive with antibodies directed against
c-fos, c-jun, and both osteopontin and osteocalcin as well a type-1 collagen
Ultrastructure: Myofibroblasts as well as fibroblasts are seen in the collagenous
background. The osseous component contains immature woven bone lined by abnormal osteoblasts with
fibroblast-like appearance. Other cells are noted to have large microfibrillary ctyoplasmic brush
borders . Intracytoplasmic myofibrils have also been
The prognosis of patients with FD is quite good. Malignant transformation occurs but is rare. Some
lesions have been reported to heal spontaneously .
Symptomatic circumscribed lesions require curettage, cryosurgery and/or bone grafting
 and many individuals have received chemotherapeutic rather than surgical
approaches. Radiation to bone affected by FD may result in post-irradiation sarcoma
. Spontaneous development of sarcoma in FD bone has an ominous prognosis
often with rapid progression as in this case.
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