CASE 8
DIAGNOSIS: OSSIFYING FIBROMA, JUVENILE PSAMMOMATOID
VARIANT
CLINICAL HISTORY:
A 14 year old girl with a history of chronic headaches presented with an acute
exacerbation of a right sided headache with associated sinusitis. Associated symptoms
included photophobia. A sinus CT scan identified a 1 cm osseous lesion located at the
right frontoethmoidal sinus complex. The patient subsequently underwent endoscopic
stereotactic-guided sinus surgery with complete removal of the tumor.
DISCUSSION:
Benign fibro-osseous lesions (BFOLs) of the craniofacial bones comprise a diverse group
of clinicopathologic entities and include developmental, neoplastic and reactive
processes. The recognized BFOLs are fibrous dysplasia, ossifying fibroma (and its
variants) as well as the osseous (cemento-osseous) dysplasias. All BFOLs are
characterized by the replacement of normal bone by fibrous connective tissue with
varying degrees of mineralized components including osteoid, bone and cementum-like
calcifications. As such, the histologic diagnosis is relatively straightforward; the main
challenge lies in the subclassification of these entities. In addition, other processes may
mimic BFOLs such as chronic osteomyelitis, central giant cell lesion, renal
osteodystrophy, osteoblastoma and osteosarcoma.
Clinically, BFOLs may present with pain and expansion of the jawbones or may be
asymptomatic and found incidentally on imaging studies. For most of the subtypes, there
are rather distinct clinical and radiologic findings. Because of the significant histologic
overlap among the BFOLs, the diagnosis rests on the constellation of clinical, radiologic,
operative and histologic findings. If these are not available and one is dealing with a
BFOL, the pathologist should diagnose the lesion as “benign fibro-osseous lesion” with a
comment.
Ossifying Fibroma
Ossifying fibroma (OF) is considered a true neoplasm of the jaws and, less commonly,
other craniofacial bones. OF was previously thought to originate from cells of the
periodontal ligament, but, this does not explain tumors arising in non-tooth bearing
bones. There is a slight female predilection and most occur in the third and fourth
decades. Conventional OF more frequently arises in the mandible (70%) with a
predilection for the posterior elements in both jaw bones. They are usually slow growing
tumors that expand the involved bone and average about 3-4 cm. Others can be quite
large resulting in marked facial distortion.
Radiologically, OF appear as unilocular lesions with sharply demarcated and smooth
borders. Early lesions are radiolucent and, depending on the amount of calcification,
older lesions may have a mixed radiolucent and radiopaque appearance. Because OF are
sharply demarcated from the native bone, the surgeon typically is able to shell the lesion
out easily.
Histologically, OF are demarcated from the uninvolved native bone lacking evidence of
fusion with the cortex. OF usually have a variegated microscopic appearance with
varying amounts and quality of connective and mineralized tissues. The stroma is
moderately cellular and comprised of bland spindle-oval fibroblastic cells. The cells can
be haphazardly arranged or grow in short fascicles and even storiform patterns. The
mineralized tissues can be trabeculae of woven bone, trabeculae or larger zones of
lamellar bone, and/or round/ovoid calcium deposits resembling cementum (hence the old
term “cemento-ossifying fibroma”). These calcified spherules often coalesce to form
nodules. Most OF consist of a haphazard mixture of these mineralized elements.
Osteoblastic rimming can be seen in any of these mineralized deposits.
Most lesions can be surgically excised completely with curettage or enucleation.
Recurrence is rare with conventional OF.
Juvenile Ossifying Fibroma
A subset of OF have distinct clinical and histologic findings and have been termed
juvenile OF (JOF). There are two recognized subtypes, the psammomatoid and
trabecular variants. Psammomatoid juvenile OF (PJOF) is more common than trabecular
juvenile OF (TJOF). Both can be seen in patients of any age, however, most arise in
patients in the first and second decades. PJOF tends to occur in slightly older individuals
(mean 20 yrs) than TJOF (mean 9-12 yrs). There appears to be no sex predilection for
JOF. PJOF most often arises in the orbit, paranasal sinuses and calvaria (75%) with the
remaining 25% occurring in the maxilla and mandible. In contrast, TJOF usually
develops in the jawbones (95%) with a predilection for the maxilla. Imaging findings are
less specific but most are mixed radiolucent and radiopaque and are well-demarcated.
Histologically, PJOF consists of a cell rich, paucivascular stroma with little collagen.
The cellularity tends to be uniform and the matrix also tends to be of uniform
composition and distribution. The mineralized elements consist of basophilic, acellular
or paucicellular, round/oval structures imparting a superficial resemblance to psammoma
bodies. TJOF consist of a variably cellular stroma with plump spindle cells associated
with varying amounts of collagen. In the cellular areas, condensation of plump
osteoblasts associated with thin seams of osteoid can be identified. These appear to
mature to progressively larger trabeculae of woven bone lined by osteoblasts. Occasional
cases also may have trabeculae of lamellar bone and calcified spherules. Myxoid
degeneration, aneurysmal bone cyst changes and multinucleated giant cells may be seen
in both variants.
Conservative resection is the treatment of choice with recurrence rates ranging from 30-
50% (hence the previous name “aggressive JOF”). Transformation into a sarcoma has
not been reported.
Fibrous Dysplasia
Fibrous dysplasia (FD) is a fibro-osseous lesion likely arising from altered
osteoprogenitor fibroblast-like cells. FD typically arises in the first or second decade as a
slowly enlarging painless expansion of the involved bone(s). There is no sex or rade
predilection. Lesions tend to stop growing at the onset of puberty or skeletal maturation.
FD can be classified into monostotic, polyostotic, craniofacial and syndromic types. The
syndromic types arise with polyostotic FD and include McCune-Albright syndrome (triad
of polyostotic FD, café au lait spots and multiple endocrinopathies) and Mazabraud
syndrome (polyostotic FD and intramuscular mxyomas). All types are associated with an
activating mutation of the GNAS1 gene (alpha subunit of a G stimulatory protein) on
chromosome 20q13 resulting in constitutive activation of adenylyl cyclase leading to a
persistent increase in cAMP which, in turn, activates one or more downstream genes.
Approximately 25% of patients with FD have involvement of the craniofacial bones.
Craniofacial FD is used to describe maxillary FD because there is often continuous
involvement of adjacent bones such as the zygoma, sphenoid, temporal, orbital, and
frontonasal bones. Because of this, they are not considered true polyostotic FD.
Although multiple contiguous bones are often involved, craniofacial FD is usually a
unilateral process. Mandibular FD can be monostotic or polyostotic.
The radiologic appearance is characteristic and varies with the stage and amount of
mineralized matrix. Early lesions are lytic but the classic finding in established lesions is
a ground glass appearance with indiscernible borders that blend into the adjacent
uninvolved bone. This contrasts with the imaging findings of OF and is very helpful in
the differential diagnosis of these two. Radiolucencies may develop and are typically
associated with secondary aneurismal bone cyst changes. At surgery, the abnormal bone
is difficult to separate from native bone and is often received as gritty fragments.
The histologic appearance of FD depends on the stage of the lesion and FD of the
craniofacial bones can show changes that are not seen in other bones. Early FD is
characterized by irregular (curvilinear; Chinese characters) trabeculae of woven bone
associated with a moderately cellular, haphazard proliferation of bland spindled-ovoid
fibroblasts. Lesional bone fuses with adjacent non-lesional bone. Unlike in the long
bones, FD of craniofacial bones can undergo maturation to lamellar bone with a decrease
in stromal fibroblast cellularity. Other changes that may be seen that are not seen in long
bone FD include prominent osteoblast riming and cementum-like calcifications. One
feature that is seen in FD but typically not in OF is histologic uniformity from field to
field within a given tumor. In contrast, OF demonstrate histologic variety with differing
amounts and quality of both the fibrous stromal and mineralized elements.
Osseous Dysplasia
While osseous dysplasias (OD) are the most common of the BFOLs, they are the least
likely to be seen as a surgical pathology specimen. They include both non-hereditary
(reactive) and hereditary forms. These lesions occur only tooth-bearing bones and are
likely related to the periodontal ligament structures. Because of the distinct predilection
for women, hormone-related abnormalities may play a role in OD pathogenesis. The OD
subtypes include periapical, focal, florid and familial gigantiform cementoma (FGC).
Each type has unique demographic, radiologic and clinical features which allow for their
distinction (Table). However, they all appear similar histologically consisting of
“dysplastic” or disordered production of bone/cementum and fibrous tissue. The
histologic features overlap with OF and FD and depend on the stage of the lesion. Early
lesions contain a more cellular spindle cell fibroblastic stroma with varying amounts of
cementum-like calcifications and trabeculae of woven bone. In older lesions, calcified
matrix elements predominate with less cellular and more collagenized stroma. Lamellar
bone with Paget-like reversal lines may be seen and stromal multinucleated giant cells
can be seen in any stage of the lesion. Compared to OF and FD, the stroma tends to be
more vascularized. OD usually do not require surgical intervention but do require
follow-up to monitor growth of the lesions. In the rare cases that do go to surgery, the
lesion tends to be removed as gritty fragments that are hard to separate from the native
bone, similar to FD, but unlike OF which shells out easily.
Age Race Symptoms Focality Location Expansion
Periapical 30-50 B>>>>W None Uni- or multifocal Ant mand No
Focal 30-50 B>>W None Unifocal Post mand No
Florid 30-50 B>>>>W Pain, none Multifocal; 2+ quadrant Post mand No; Minor
FGC Young B=W Pain, none Multifocal; 2+ quadrant All Yes
Differential Diagnosis of BFOLs
Several pathologic processes that involve the jawbones can have some histologic, clinical
and radiologic overlap with the BFOLs. These include neoplastic (benign and
malignant), inflammatory, metabolic and other giant cell rich lesions. Neoplastic lesions
include low-grade osteosarcoma, osteoid osteoma, osteoblastoma/cementoblastoma,
intra-osseous meningioma and odontogenic fibroma. Several forms of chronic
osteomyelitis can involve the jawbones inducing a fibro-osseous response. The presence
of inflammatory foci should raise this possibility, especially if a history of tooth abscess
or prior surgery is identified. Chronic renal failure or parathyroid disease should raise the
consideration of renal osteodystrophy and brown tumor, respectively. Paget disease of
bone can histologically resemble BFOL but has characteristic clinical and radiologic
findings. Finally, some giant cell lesions such as central giant cell lesion (formerly giant
cell reparative granuloma), cherubism and aneurysmal bone cyst can have a more fibrous
spindle cell stroma with reactive bone formation.
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