Fib ro-osseou s and
os te ochond rom at ou s l es io ns
Ossifying flbroma
E I- Mott y S . K .
Nelso n B .
Toyosawa S.
Definition
O ssify ing f i b romas are ben i g n fibro­
osseous neoplasms affecti n g the jaws
and the craniofaci al skeleton . The three
clinicopathological variants that have
been identified are ossifyi ng fibroma of
odontogenic ori g i n - also call ed cemen­
ta-ossifyi ng fibroma (COF) - and two dis­
tinct juvenile ossifying fibromas: j uvenil e
trabecular ossifyi n g fibroma (J TO F) and
juvenile psammomatoid ossifying fibro­
ma (J POF) (632 , 2208) .
IC D-0 code
Ossifying fi broma 9262/0
Synonyms
Cementa-ossifying fi b roma: central os­
sifying fi broma; cementifyi ng fibroma;
perio dontoma
Juvenile ossifying fibroma: j u venile active
ossifying fibroma; juvenile aggressive os­
sifying f i broma
Epidemiology
COF is rare . The peak incidence is in the
third and fourth d ecades of life. There
is a definite female predil ection, with a
fem ale -to-male ratio as h ig h as 5 : 1 (638,
674 ).
JTOF is a rare bone tumour. It predo-
Fig. 8.88
Cemento-ossifying fibroma. Radiog raphy
sh�wing a well-
defined, expansive radiol ucent lesion with
rad1odense areas
present in the mandibular molar area.
Fig. 8.89 Juvenile trabecular ossifying fibroma .
CT showing a circumscribed, expansive lesion of the
maxilla; cortical thinning is observed.
mi nantly affects children and adoles­
cents, with a mean pati ent age of 8. 5-
1 2 years (632). The sexes are equally
affected .
J POF i s a rare tumour. The reported
mean patient age ranges from 1 6 to 33
years. However, the overall patient age
rang e is wide; cases have been reported
in patients as young as 3 months and as
old as 72 years (632,638 , 22 1 4). There is
no sex predilection .
Local ization
COF occurs exc lusively in the tooth­
bearing areas of the mandible and max­
illa. The mand ible is far more commonly
involved than the maxilla. The mandibu­
lar premolar and molar area is the most
common site.
cl;·
fibroma . A Bone trabeculae _ and ce�entum-like tiss �e i� a fibroblastic stroma.
Fig. 8.90 Cemento-osslfyln�
the lesion 1s well defined and abuts the cortical bone, the cementum-like tissue is dominant in this
8 The periphery of
lesion.
Fibro-osseous and osteochondromatous lesions
Fig. 8.91 Juvenile psammomatoid ossifying fibroma.
CT shows an expansile, well-defined, but incompletely
corticated lesion with ground-glass appearance at the
ethmoid area .
JTOF occurs in the maxilla and mandible,
with the maxilla being a more common
site. Extrag nathic occurrence is extreme­
ly rare.
J POF may occur in the jaws but it pre­
domi nantly affects the extragnathic cra­
niof acial bones, particularly the periorbi­
tal frontal and ethmoid bones (632).
Cli nical featu res
COFs present as a painless expansion of
the buccal and l ingual plates of the af­
fected bone. Large lesions can expand
the inferior border of the mandible or the
floor of the maxil lary sinus. Radiographi­
cal ly, early lesions are typical ly radiolu­
cent. Over time, the tumour becomes
progressively more radiopaque (638,
676 , 2208) . JTO Fs are characterized by
;:,,.) . ' ..
251

F ig. 8.92 Juvenile trabecular ossifying fibroma.
B Aggregates of osteoclast-like cells.
progressive and sometimes rapid expan­
sion of the affected bone. I n the maxilla,
obstruction of the nasal passages and
epistaxis can occur. Radiographical ly,
the tumour is expansile and fai rly well d e ­
marcated . It m ay be rad iolucent or may
show various d eg rees of opacificatio n .
C ortical t h i n n i n g a n d perforation c a n oc­
cur {632 , 2 2 1 3}.
J PO Fs p resent as bony expansions that
may i nvolve the orbit or nasal bones and
sinuse s . Tum o u r expansion can result i n
p ro ptosi s , visual symptoms, a n d nasal
obstructio n . The rapid tumour g rowth
that has been obse rved in some cases
is most l ikely caused by second ary an­
eu rysmal bone-cyst formation {632,638).
M acroscopy
An important feature of C O F is that it
is well d efined and can be shelled out
relatively easily from the su rroun d i ng tis­
sue. G rossly, the tumour is subm itted in
one piece o r i n large frag ments that are
yel l owish-tan and m ay be haemorrhagi c
and feel g ritty when c u t with a scalpel
{638,676). O n cut su rface, J TO F shows
curvilinear haemorrhagic strands not
seen in other types of ossifyi ng fi broma
{2210}.
Histopathology
COF is well defined and may be en-
Fig. 8.93 Cut surface of specimen of juvenile trabecular
ossifying fibroma. Curvilinear haemorrhagic strands
create a distinct pattern typical for this lesion.
252 Odontogenic and maxil lofacial bone tumours
capsulated . It is composed of hyper­
cellular fibroblasti c stroma containing
variable amounts of calcified structu res .
The stromal cells have hyperchromatic
nuclei but no marked atypia. M itosis is
not easily fou n d . The calcified structures
are com posed of variable amounts of os­
teoid or bone and lobulated basophilic
masses of cementum-like tissue. These
stru ctu res may coalesce and form curvi­
linear trabeculae, which may be acellular.
The ratio of bone to cementum-like tissue
varies from lesion to lesion; in some tu­
mours, one type of calcified tissue may
dominate. Osteoblastic rimming of the
bone trabeculae is evident. Polarized
light microscopy shows both woven and
lamellar bone. The cementum -like tissue
is often woven , and may show a charac­
teristic qui lted pattern .
JTOF is unencapsu lated but neverthe­
less maintai ns a wel l-deli neated border.
It has a characte ristic loose arch itectu re ,
with hypercell ular stroma composed of
spindle cells with little collagen produc­
tion . Osteo id develops directly from the
fibrous stroma and forms long slender
strands that have been likened to paint
brush strokes. Irregul ar mi neralization
takes place at the centre of the strands,
resulting in the production of immature
bone trabeculae that are devoid of osteo ­
blastic rimming and show no evidence
of matu ration. Aggregates of osteoclas­
tic giant cells are typically found in the
stroma. Occasional mitoses may be ob­
served i n the stromal cells. Aneurysmal
bone-cyst formation has been reported
in some cases !632, 2208 , 22 1 3 ) .
JPO F i s unencapsu lated and is charac­
terized by multiple small uniform ossi­
cles (psammomatoid bodi es) embedded
in cellular stroma composed of spin­
dled and stellate cells !632,638 , 2 2 1 4 ) .
T h e psammomatoid bodies are baso­
philic and bear some resem blance to
-
.. . � �� .
�Si. -
Fig. 8.94 Juvenile psammomatoid ossifying fibroma.
Small uniform round ossicles (psammomatoid bodies) in
fibroblastic stroma.
dental cementum. At the periphery of the
lesion, these structures may coalesce
and form bone trabeculae. Cystic degen­
eration and aneurysmal bone-cyst forma­
tion may occ u r.
Genetic profile
M utations in COC73 (also called HRPT2)
have been reported in sporadic cases
{53 7,1 890). C O F lacks the GNAS gene
mutation that is characteristic of fibrous
dysplasia.
Genetic suscepti bility
M u ltiple ossifying fi bromas may be as­
soc iated with hyperparathyroidism-jaw
tumour syn d rome, which is caused by
CDC73 (also called HRPT2) mutations
1340). Les ions with s i milar histolog ical
featu res have been repo rted in a famil ial
setti ng as gigantiform cementoma (see
next section) 1 63 4 ) .
Prog nos is a n d pred ictive factors
COF is a slow-g rowing benign neopla sm.
It can be surg ically excised conservative­
ly, with no recu rrence in most cases . Un­
treated tumours can atta i n a massive size
and may require en bloc resection. Sar­
comatous transformation has not been
documen ted 1633,638, 674 ) .
Multiple rec urrences have been reported
fol lowing conservative excision of both
JTOF and J PO F. Malig nant transform -
tion has not been reported 1632).
fsmifisl gigsntiform
osmsntoms
EI-MoftY S.K.

Defin itio n
gig ant1fo rm cementom a ( F GC)
Fa rn ilia l
. ra re form of fibro -osseous lesion of
is a .
h · haracterize d b y ear I y o nset of
t e J aws c . .
ult1 q u a d ran t p ro g ressive I y
rnu lt ifo cal/m ·
·
pa n sive lesi ons t h at may b e massive
dispersed in a fibroblastic stroma. B Basophilic hypocellular curvilinear cementum-like tissue
:�d ca us e remarkab le facial defo rmity.
N o oth er bones �re aff� cte d . Auto so-
al do m in ant inheritance 1s seen among and extensive i nvolvement of the jaws. Definition
:rn e cases whereas others are famil ial . Simple cosmetic recontouring proce­ Fibrous dysplasia (FD) is a skeletal
�po ra dic cases without known herit able d u res result in recurrences, which may anomaly in which normal bone is re­
featu res have also been d escribe d . be multiple and occasionally at a more placed and distorted by poorly organized
accelerated rate (3A,634,676,21 38A). and i nadequately mineralized immatu re
bone and fi brous tissue. It may involve a
single bone (monostotic FD) or multiple
Fibrous dysplasia bones (polyostotic FD). A variety of endo­
crinopathies accompany polyostotic FD
EI-Mofty S . K . in McCune-Albright syndrome. Although
Ne lson B . FD occurri ng in multiple adj acent cranio­
Toyosawa S . facial bones is considered to be monos­
totic, the term "craniofacial fibrous dys­
plasia" is preferred for such cases (2523).

Fig. 8 .95 Familial gigantiform cementoma i n a 3-year­

old female patient. CT scan showing bilateral, massive
expansive masses of the maxilla and mandible with well­
circumscribed borders presenting as radiolucent areas
containing radiopaque calcifications.

H isto pathology
Th e m icro scopic features of FGC are
analog ous to those of cementa- ossifying
fi bro ma chara cterized by hypercell ular fi­
brobl as ic stroma with monomorp hic ap­
pearing spindle shaped fi brobl asts and
co ll ager fibres. D ispersed thro u g h o ut
the stror'l a are mi neral ized structu res of
i m m atu re bone trabeculae and cem en­
tum- like 11ssu e. The latter is formed of
hy poc el ular basophilic and curvi l i near
struc tures resembling cemen ticles that
are n orm ally seen in the periodo ntal liga­
� en . U nde r polarized light, S harpey' s
fi b re s are seen
to project rad i ally from
these sp he
roi dal deposits .
Pro g n o sis a
nd predictive factors
Su rgi cal m
ana gement of FGC is a c hal­
l en g e d u
e to ra pid reg rowth of the lesion s
Fibro-osseous and osteochondromatous lesions 253
Synonym
Craniofacial fibrous dysplasia
Epidemiology
FD accounts for approximately 7% of all
benign bone tumours {61 8}. It appears
to be a d isorder of growi ng bones; most
cases are initially identified in children
and adolescents. Monostotic FD is 6-1 0
times as common as polyostotic FD
( 735}.
Etiology
FD is caused by postzygotic activating
mi ssense mutations i n the GNAS gene,
which encodes the alpha subunit of the
stimulatory G protein (G s-alpha) { 1 86,
2 1 58 , 2575}. Constitutively active G s ­
alpha stimu lates adenylyl cyclase activ­
ity, resulting in overexpression of cA M P
a n d subsequent changes i n t h e proper­
ties of bone osteoprogenitor cells, lead­
ing to abnormal bone formation { 1 989,
1 990,1 99 1 }.
Localization
The milder forms of FD affect only a few
bones (usually asymmetrically), localized
to one region of the body. The cranio­
facial bones and the femur are the two
most common sites of both monostotic
and polyostotic FDs, but any bone can
be affected {735}. In the gnathic bones,
FD occurs more often i n the maxi l la than
in the mandible, and may exte nd to in­
volve adjacent bones such as the zygo­
matic and sphenoid bones {2523}.
Clinical features
The initial prese ntation usually consists of
pain less swelling of the jawbones, often
leading to facial asymmetry. The disease
is typically diagnosed within the first two
decades of l ife {2523}. Jaw i nvolvement
may lead to d isplacement of teeth and
malocclusion, although the dental arc h
is general ly maintained {35}. Cases af­
fecting the paranasal sinus, orbits, and
foram ina of the base of the skull can pro­
duce a vari ety of symptoms, i ncluding
nasal obstruction, visual loss, headache,
and hearing loss { 634}. I n McCune­
Albright syndrome, cafe-au-lait skin pig­
mentation and endocrine ab normalities
are present {6 1 8 }.
The radiographical appearance of FD
depends on the stage of development.
Early lesions may appear radiolucent,
whereas later lesions may appear scle­
rotic. Classic lesions typically have a
254 Odontogenic and maxil lof acial bone tumours
groun d -g lass appearance, with indistinct
borders that blend imperceptibly with the
surrounding uninvolved bone {596). In af­
fected jaws , narrowing of the periodontal
l igament spaces and effacement of the
lamina dura su rrou nding the teeth are
suggestive of FD.
Macroscopy
The affected bone is rubbery, compress­
ible, and greyish-white, with a gritty tex­
ture when cut with a scalpel .
H istopathology
The lesions consist of fib rous and osseous
tissue in varying proportions depending
on the disease stage. The fibrous tissue
consists of bland fibrob lastic cells. Mitotic
figures are uncommon. The osseous tis­
sue is composed of irregularly shaped tra­
beculae of immature woven bone without
osteoblastic rimming {41 ). These trabecu­
lae often assume curvili near forms, which
have been likened to Chi nese characters
in appearance. The lesional bone fuses
with the adjacent normal bone 141 , 2209).
Unlike FD in long bones, craniofacial le­
sions may undergo progressive matura­
tion to lamellar bone {2209, 2523}. A small
proportion of cases contain nodules of
hyaline cartilage. Cases with abu ndant
cartilage have been termed fi brocartilagi­
nous dysplasia { 1 098}.
Genetic profile
Activating mi ssense mutations in the
GNAS gene have been detected in mon­
ostotic and polyostotic FDs, as well as in
McCune-Al bright syndrome.
Prognosis and predictive factors
I n most cases, the lesions seem to sta­
bilize with skeleta l matura tion; therefo re,
surgic al intervention in young er patien ts
Fig . 8.99 Cemento-osseo s dys plas la.
� Radiography shows
cementa-osseous dysplasla in both quadran
ts of the man dibl e
shoul d be delaye d for as long as p oss ib le
{252 3). S i m ple contouring of the_ affe cte d
fac ial or skull bones to norma l dime ns io n
has prove n to be adequate . Very rarel y,
sponta neou s malig nant transfor mati on
occ urs {2027).
Cemento-osseous dysplasia
EI-Mofty S . K .
Nelson B .
Toyosawa S .
Wright J . M .
Defin ition
Cemento-osseous dysplasia (COD) is a
non-neoplastic fi bro-osseous lesion of
the tooth-beari n g regions of the gnathic
bones.
Synonyms
Osseous dysplasia; cementa! dysplasia;
ceme ntoma
Epidem iology
C O D is the most common benign fi bro­
osseous lesion of the jaws. There is a
strong predi lection for m iddle-aged
Bl ack women; an age-adjusted preva­
lence rate of 5 . 5 % among B l ack females
has been reported {62,529 , 2 1 27}.
Localization
COD occurs exc lusively i n he oath­
bearing regions of the jaw s .
Clin ical feat u res
COD has trad itiona lly been d ivided into
three varia nts (larg ely o n the basis of ana­
tom ical locat ion): peria pical C O D i s asso­
ciated with the apic al area s of man dibula r
ante rior teeth ; foca l C O D i s asso ciate d
les ,ions of mi xed
radiol uce nt and rad
. iopaque Oorid

with a single tooth; and florid COD has
multifocal (multiquadrant) involvement.
The lesions are usually asymptomatic
and may only be discovered on routine
dental radiographs /1791). COD is as­
sociated with vital teeth; however, it may
also be found in edentulous areas. The
lesions are generally non-expansive, but
florid cases are the exception; they may
be expansile and present with pain and
discharge secondary to infection /529,
1316).
Radiographical evaluation of COD is es­
sential. Ideally, these lesions should be
identified clinically and radiographically,
without the need for biopsy. The lesions
may be radiolucent, radiodense, or mixed.
Serial radiographs may show increased
density and calcification as a lesion ma­
tures. A focus of COD is generally well de­
fined and demonstrates a thin radiolucent
rim. The periodontal ligament should ap­
pear intact, and the lesion should not be
fused to the roots /529,634,1316).
Macroscopy
The lesions are grossly fragmented, grit­
ty, and tan and brown.
Histopathology
All the variants of COD have analogous
microscopic features, characterized by a
variably cellular fibrous stroma with areas
of swirling and/or loose collagen. Within
the stro ma are mineralizing tissues con­
sisting of osteoid, bone, and cementum­
like material. As the lesions mature, they
become increasingly calcified [1316}.
D ens e hypocellular sclerotic masses
rnay form, especially in florid COD. Os­
te oblastic rimming is generally rare. The
vascularity is pronounced and results in
fre e blood within biopsied specimens.
No capsule is identified. Inflammation
may be seen in cases of florid COD that
become infected {634).
Cystic changes
�ese mbling simple bone cyst may occur
in florid cases.
Prognosis and predictive factors
Once a diagnosis of periapical and focal
COD has been established, patients re­
quire no treatment and can be monitored
during routine dental appointments. Indi­
viduals with florid COD may require close
clinical follow-up for complications of os­
teomyelitis /529,1316).
Osteochondroma
Toner M.
van Heerden W.F.P.
Definition
Osteochondroma is a cartilage-capped
bony projection arising on the external
surface of bone, continuous with under­
lying bone. Categorization as a benign
neoplasm rather than a reactive lesion is
favoured 12023).
ICD-0 code 9210/0
Synonym
Osteochondromatous exostosis
Epidemiology
Osteochondroma is one of the most
common lesions of the axial skeleton but
is much rarer in the maxillofacial bones,
because it occurs at sites of endochon­
dral ossification, which are limited in this
region. Less than 1% of all osteochon­
dromas occur in the head and neck.
Osteochondromas in the maxillofacial
bones occur in the fourth to fifth dec­
ades of life, which is later than elsewhere
in the body.
Etiolo gy
Trauma may be an etiological factor
(2023). An association with external ra­
diation therapy in childhood has been
suggested.
F ibro-osseous and osteochondromatous lesions
Localization
The reported sites are the skull base,
maxillary sinus, zygoma, and mandible
(condyle and coronoid processes).
Clinical features
The symptoms are related to tumour lo­
cation. Asymmetry, malocclusion, pain,
and limited mouth opening are the most
common features of cases in the mandi­
ble 12023). Imaging reveals a lobulated
bony outgrowth in continuity with the
cortex and medulla of the bone of origin,
with a thin cartilaginous cap (although
the cap is not always visible).
Macroscopy
Osteochondromas can be sessile or pe­
dunculated.
H istopathology
The tumour consists of perichondrium
covering a hyaline cartilaginous cap and
bony stalk [2010). The cartilaginous cap
is typically < 2 cm in thickness. The oste­
ochondral junction resembles the growth
plate, and the zone of endochondral os­
sification matures into cancellous bone.
There is minimal atypia, and binucleated
forms are rare. The cortex and medulla
are continuous with the underlying bone.
Absence of BCL2 expression may be
helpful in distinguishing osteochondroma
from chondrosarcoma (925).
Genetic profile
Homozygous deletion of the EXT1 gene,
located at 8q22-24.1, occurs in chon­
drocytes in sporadic osteochondromas.
Abnormalities of both EXT1 and EXT2 are
associated with hereditary multiple os­
teochondromas [2010).
Genetic susceptibility
About 15% of patients with osteochon­
dromas have hereditary multiple osteo­
chondromas/exostoses, but this condi­
tion rarely involves the maxillofacial
bones [2010}.
Prognosis and predictive factors
Excision is curative, although recurrence
is possible following incomplete removal
Malignant transformation is very rare
255
 G i a nt cel l lesions and bone cysts
Central giant cell granuloma
Raubenheimer E.
Jordan R.C.
Defin ition
Central gi ant cell granuloma (CGCG) is a
localized, benign but sometimes aggres­
sive osteolytic lesion of the jaws charac­
terized by osteoclast-type giant cells in a
vascular stroma.
Synonyms
Central giant cell lesion; reparative giant
cell granuloma (obsolete)
Epidemiology
CGCGs account for 1 0% of benign gnath­
ic tumours. Most cases occur in females
and in patients aged < 20 years { 729}.
Local ization
The lesions are more frequent i n the ante­
rior jaws , in particu lar the mandible. Mul­
tiple lesions should raise suspicion for
Noonan syndrome, LEOPARD syndrome,
or neurofi bromatosis type 1 {2492}.
Clin ical features
CGCGs generally present as slow­
growing , asymptomatic, expansile, well­
defined rad iolucencies, without tooth
Fig. 8.1 01 Central giant cell granuloma presenting as a
well-circumscribed radiolucency in the anterior mandible.
256 Odon ogenic and max11lofacial bone tumours
Fig. 8.102 Central giant cell granuloma. Occlusal
radiograph showing mandibular expansion and
tooth displacement in a multilocular central giant cell
granuloma.
resorption. More advanced lesions may
be multi locul ar. About 30% of cases fol­
low an aggressive clinical cou rse char­
acterized by pain, tooth resorption and
dis placement, cortical perforation, and
invasion of perignathic tissues 12492}.
M R I and PET-CT are helpful in delineat­
ing soft tissue involvement and multicen­
tricity, respectively ( 1 572) .
Macroscopy
The lesion has a fleshy, reddish-brown,
haemorrhag ic appearance.
Histopathology
CGCG is characterized by an unencap­
sulated prol iferation of mononuclear
spind le-shaped and polygonal cells with
osteo clast- type m u ltin uclea ted g i an ce s
in a vascula r backgr oun d , with hae m cr­
rhage and haemo siderin pigmen . T e
lesion may have a lobular archi ec u'e
separa te d by fibrous septa with os eo �
and woven bone. Other g iant cell l esio s
with similar featu res (such as cherub is ,,
hyperparathyroidism , and aneurys ma
bone cyst) m u st be exclu d e d . The g -
ant cells in C G C G s show reactivity for
osteoclast and macrophage mar kers
( 729, 241 3 , 2492 ) . The mononuclear s ro­
mal cell is the p roliferative componen .
Genetic profile
CGCG does not have a defined genetic
profile, and lacks the point m utations in
the histone H3F3A gene that character­
ize giant cell tumour of bone { 1 922).
Genetic susceptibil ity
M ost CGCGs have no genetic asso­
ciation, but a mi nority of cases (most
commonly cases associated with neu­
rofibromatosis type 1 , N oonan syn­
drome, or LEOPA R D syn drome) arise in
patients with germline m utations in the
genes encod i n g specific proteins of the
RAS/MAPK pathway ( 729,1 723).
Prognosis and predictive factors
Most CGCGs respond favourably to lo­
cal curettage. A higher recurrence rate
is as so ciat ed with an aggre ssive clini­
cal co urse { 2492} a n d associ ation with
N oon an syndro me or neurof ibro mato sis
type 1 1729}. To l i m it the extent of resec­
tion of larg e lesions, intrales ional or sys­
tem ic pha rmacological agents such as
steroi ds, calcitonin , interfe ron , and the
R A NK ligan d i n h ibitor denosu mab may
be considered 1 54 , 2492} .

Peripheral giant cell granuloma

Peripheral giant cell granuloma. A Manifesting as a broad-based non-ulcerated polyp on the alveolar
mucosa of the right mandible. B Cut surface of an excision specimen, showing � fleshy reddish-brown appearance.

Raubenheimer E. • ��,�--�0�
Jordan R.C.

Definition
Peripheral giant cell g ranuloma is a re­
active local ized proliferation of mononu­
clear cells and osteoclast-type giant cells
in a vascular stroma outside bone. It oc­
curs in the ging iva or alveolar m u cosa.

Synonym
Giant cell epulis

Epidemiology
Peripheral giant cell granuloma is the
most common g i ant cell lesion affecting
the oral tissues {21 36}.
Etiology
The lesion occu rs as a result of local ir­
ritat ion of the m ucoperiosteum or the cor­
onal part of the periodontal ligament by
dental calcu lus deposits or other types of
chronic irritation {388).
Loc aliz atio n
Perip heral giant cell granulom a is more
com mon in the ging iva and edentu lous
alveol ar ridge of the mandib le, but can
also affe ct the maxilla (2 1 3 6).
Clin ica l features
The p roliferation presen ts as a sessile or
Pe du ncu lated soft-pin k to purplis h-bl ue
lump w ith a smooth , ulcerated, or papil ­
lom atous surface ( 2 1 36}. A sh al low in­
de ntatio n of the adjacent alveo lar bon e
may be p resent 1388).
M ac roscop y
Du e to vascularity, the cut s urface of the
speci me ns often has a flesh y redd ish­
brow n app earance.
H�stopathology
Histology shows
an u n enca psul ated
proliferation of mononuclear spindle­
shaped and polygonal cells with giant
cells in a vascularized background. Foci
of haemorrhage, haemosiderin pigment,
and scattered deposits of immature bone
are freq uent.
Prog nosis and pred ictive factors
Surg ical removal is advised , and the
recurrence rate is low. The lesions may
even reg ress after removal of the irritant.
Cherubism
Jor dan R.C .
Ra ube nhe ime r E.
Defin itio n
in-
Che rubi sm is an auto som al dom inant
ed by sym ­
her ited con ditio n cha rac teriz
max illa and
met rica l exp ans ion of the
by cyst-like
man di ble as bon e is repl ace d
and gia nt cel l les ion s ( 729 ).
Syn onym s . . . .
nile fi brous
Fam il ial fi brou s dys plas 1a; Juve
(bo th term s are obs olet e)
dys pl asia
Giant cell lesions and bone cysts
Ep idemiology
The incidence of cherubism is un known
but the condition is rare {367}. Cherub�
ism presents in childhood or preadoles­
cence and is most often followed by par­
tial or complete reg ression in adulthood.
Most cases are familial, with variable
penetrance and expressivity. De novo
cases from sporadic m utations can also
occur.
Etiology
Mutations of the SH3BP2 gene, located
on chromosome 4p1 6.3, have been iden­
tified in about 80% of cases of cherub­
ism (1 523). The majority of m utations
occur i n exon 9 , within a praline-rich se­
quence 6 amino acids long, resulting in a
constitutively active form that increases
the activity of osteoclasts {2443}.
Local ization
Both jaws are affected bilaterally, with
the mand ible affected more exten sively
.
than the maxilla. The condition appears
to start around the fi rst molars, but typi­
cally spares the condyles. In the maxilla
cherubism begins in the tuberosity and
subsequently affects other areas.
257
Fig. 8.106 Cherubism. A A child showing bilateral maxillary and mandibular bone expansion, with malpositioned and
displaced teeth. B Panoramic radiograph showing multifocal radiolucent lesions of the maxilla and mandible, with
missing and displaced teeth.
Cli nical features
Slow, symmetrical expansion of the jaws
occurs before the age of 6 years. Expan­
sion of the maxi lla may cause retraction
of the facial skin, including the eyelids,
lead ing to scleral exposure and the char­
acteristic so-called heavenly gaze, which
is similar to the facial appearance of putti
(angelic children) in Renaissance pai nt­
ings (incorrectly referred to as cherubs
in the Baroq ue period of art). Females
are typically more severely affected than
males 1 1 92 1 ) . Bone expansion leads to
tooth displacement, altered tooth erup­
tion, loosening of teeth, speech altera­
tion, and visual impairment 1 1 921 }. Ra­
diographicall y, the affected bones have
a m ultilocu lated, so-called soap-bu bble
radiol ucent quality { 1 967 ) . The cortices
may be thinned, and with time the fi brous
tissue is replaced by new bone, lead ing
to sclerosis.
Macroscopy
Similar to the appearance of other
giant cell lesions, the tissue may be red
and haemorrhagic with areas of cystic
change.
Histopathology
The histology is not specific, and may re­
semble that of other gi ant cel l lesions of
the jaws, such as giant cell g ranuloma,
Fig. 8.1 07 Aneurysmal bone cyst. A Low-power image showing blood-filled sinusoidal spaces. B High-power image showin
giant cells. C Solid type. Solid area containing clusters of multinucleated giant cells set in fibrovascular stroma.
258 Odontog enic and maxil lofacial bone tumours
showing the features of an aneurysmal bone cyst
involving the right mandible of an 8-year-old boy.
Noonan syndrome 1 1 723 1 , and t h e bone
lesions of hyperparathyroidism. Variably
cell ular mesenchymal tiss ues contain fo­
cally aggregated clusters of multinucle­
ated giant cells. Eosinoph ilic cuff-l ike
perivascular deposits can be seen, but
are not a consistent finding.
Genetic suscepti bility
The condition occurs in families and is
inherited in an autosomal dominant man­
ner 1 729).
Prognosis and predictive factors
Most cases regress after puberty 1 1 92 1 ) ,
but some cases show continued growth
with little regression 1345) . Before pu­
berty, surgery should be performed only
in severe cases, where it will provide a
fu nctional benefit.
Aneurysms/ bone cyst
Jordan R . C .
Koutlas I .
Raubenheimer E .
Definition
Aneu rysmal bone cyst (ABC) is a cystic
or mu lticystic expansile osteolytic neo­
plasm composed of blood-fil led spaces
g blood-fi1l led smuso,
Fig. 8.108 Aneurysmal bone cyst. Panoramic radiograph
separated by fibrous se pta contai ning
osteoclast-type giant cells.
ICD-0 code 9260/0
Epidemiology
ABC is rare, with an estimated annual in­
cidence of approximately 0.1 5 cases per
1 million population { 1 381 }. About 1 . 5%
of all cases occur i n the jaws. All age
groups are affected , but > 80% of cases
occur in younger patients, usually within
the first two decades of l ife . The sexes
are equally affected overal l , but a male
predil ection has been reported for cases
of the jaws { 1 663).
Localization
More than 60% of cases occur in the
mandible; more frequently in the poste­
rior regions { 1 663). Maxil lary lesions have
a more uniform anatomical distribution .
Other sites i n the craniofacial complex
can also be affected .
Clinical features
There is e nlargement, which is frequently
painful (1 663). The teeth remain vital,
but tooth mobi lity and displacement are
common. Maxillary tumours can extend
to the sinuses , nose, and orbits and can
result i n exophthalmos. Radiographically,
there is expan sion with well-deli neated
· r
'da I spaces med bY mu It'inucleated
unilocular or multilocular radiolucencies.
perforation of the cortex can occur with
extension to the adjacent soft tissues.
Root resorptiOn is seen . CT m ay reveal
bon·e septa compartmentalizing the le­
sion. CT and MRI demonstrate fluid-fluid
levels that are characteristic of (but not
specific for) ABC (2427 }.
Macro scopy
The cysts are haemorrhagic and multi­
cam eral, featuring fi brous septa of vari­
able thickness. Solid areas may be iden­
tified; these constitute either the solid
portion of the p rimary tumour or a portion
of tumour that has u n dergone second­
ary ABC- l ike changes. Rarely, the entire
lesion is soli d.
Histopathology
ABC is composed of blood-filled or
empty sinusoidal spaces that are lined
by macrophages and fibroblasts and
are separated by fibrous septa contain­
ing scattered multin ucleated osteocl ast­
like giant cells. Woven bone can appear
prominently basophilic (the so-called
blue-bone appearance), but this is not
diagnostic. The solid variant can feature
cellular areas (which may be mitotically
active) and few inconspicuous cystic
spaces. ABC-li ke areas (secondary ABC)
can occur in a variety of other disorders
of bone, i ncluding osteob lastoma, fibrous
dysplasia, and ossifying fibromas.
Simple bone cyst
Raubenheimer E.
van Heerden W. F. P.
Wright J . M.
Definition
Simple bone cyst (SBC) is an intraosse­
ous cavity that is devoid of an epithelial
lining and i s either empty or filled with se­
rous or sanguineous fluid.
Synonyms
Traumatic bone cyst; haemorrhagic bone
cyst ; unicameral bone cyst; sol itary bone
cyst
Epidemiolog y
SBCs have an equal sex distribution
and occur in young patients (in the sec­
ond or third decades of life) 1 1 025). One
third are associated with florid osseous
dysplasia in popu lations where florid os­
seous dysplasia is common /368} . An
older average patient age and a female
predominance have been reported for
SBCs associated with florid osseous
dysplasia 1368).
Etiology
The etiology is unknown. Trauma does
not seem to play a role; the incidence
in patients with a history of trauma is the
same as that in the general population
1230 1 ).
Localization
SBCs are usually solitary and typically
affect the metaphysis of long bones. I n
the head and neck region, they occur
mostly in the mandible, with a predilec­
tion for the body of the mandible / 1 025).
M ultiple SBCs account for 1 3% of cases
1230 1 ).
Cl inical features
AJthough a small number of cases mani­
fest with a pathological fracture, SBCs
are generally asymptomatic, and are
usually found incidentally during rou­
tine examination. Radiologically, they

Genetic profile
Rearrangements of CDH 1 1 and/or USP6 Fig . 8.109 Simple bone cyst cavity in the left mandible. A Note the scalloping between the roots of the associated teeth.
are seen in 69% of primary ABCs ( 1 772) B Florid osseous dysplasia with a multilocular simple bone cyst cavity in the right mandible.
but not in secondary ABCs. Other fusion
partners for CDH 1 1 include COL 1A 1,
OMO, THRAP3 (also called TRAP150),
and CNBP (also called ZNF9). Fusion
results in the upregulation of USP6. Al­
though the mechanism is not well under­
stood, USP6 upregulation may affect ac­
tin remodelling and vesicular trafficking,
which regulate cell motility and i nvasive­
ness (1550). Familial cases have been
d escribed ( 1 380). but not in the jaws or
sku ll.

Prognosis and predictive factors

AB C can be treated with curettag e, but
en bloc resection may be necessary for
l arg e, destructive tumours. The recur­
ren ce rate is approximately 1 0% , with
soft tiss ue exte nsion.
Fig . 8.1 1 0 Simple �ne cyst. Curettings of the wall of a simple bone cyst cavity showing connective tissue, lace-like
osteoid, and lamellar bone.

Giant cell lesions and bone cysts 259


are well-defi ned rad iolucencies that
freq uently extend between the roots
of associated teeth , without resorption
or displacement { 1 025). Larger exam­
ples may be multilocu lar. A minority of
cases ( 1 7.6%, 2.9%, and 1 1 . 8 % , respec­
tively) show bo ne expansion , loss of the
periodontal ligame nt space, and efface­
ment of the lami na d ura. Expansion of
he cortical plates and loss of the lami na
d ura are more frequent i n cases associ­
ated with osseous dysplasia 1368).
Macroscopy
U pon surgical exploration , the cavity
is either empty or filled with serous or
H a e m a tolym phoid tu mours
Solitary plasmacytoma of bone
Definition
Solitary plasmacytoma of bone (SPB) is
a local ized prol ife ration of monoclonal
plasma cells i nvolving bone. No oth er
bo ny lesions are present on imagi ng
studies, and there are no diagnostic cli ni­
cal featu res of plasma cell myeloma. Mi n­
imal bo ne m arrow i nvolvement (< 1 0%
plasma cel ls) m ay be seen i n a subset of
patients.
ICD-0 code 9731/3
Synonyms
Plasmacytoma of bone; osseous plasma­
cytoma
Epidemiology
SPB is rare, accounting for 3-5% of all
plasma cell neopl asms . There is a male
predominance, with a male-to-female
ratio of 2 : 1 , and the median patient age is
55 years { 1 087}.
Localization
S P B presents as a solitary bone lesion ,
with the axial skeleton ( in particular the
vertebrae) i nvolved more frequently than
the appendicula r skeleton { 1 087). I n the
head and neck region , this lesion occurs
much m ore frequent ly i n the mandibl e
260 Odonto genic and maxillo facial bone tumour s
ol ar
sangu i neo us fluid . The i nfer ior alve _
e the cavi ty
nerve is often visib le i nsid
12038).
Histopathology " . .
The term "sim ple bone cyst is i n fact
somew hat of a misn omer , beca use the
spec imens neve r have an e pithe lial l i � ­
ing . Comp resse d con nective tiss � e 1s
often seen li ni ng the cavity , sometimes
with myxom atous chang e and often with
immatu re lace-like osteoid or spiky col­
lagen deposits ( 1 6 1 ).
Prognos is and predictiv e factors
Surgical exploratio n and curettage are
..
' immu nohistochemistry or add itional stud­
Fi g . 8.1 1 1 Solitary plasmacytoma involving the mandible
of a 73-year-old man. The tumour is composed of sheets
of plasma cells.
than i n the maxilla, most common ly i n the
bone marrow-rich areas of the body, an­
gle, and ram us ( 24).
Clinical features
The most common symptoms of head
and neck SPB are pai n i n the jaws and
teeth , migration of teeth, haemorrhage ,
and swelli ng { 1 90 1 ) . A monoclonal serum
or uri ne paraprotein ( M protei n) may be
present, but hypercalcae mia, renal i ns uf­
ficiency, and anaemia are absent ( 1 087,
1 950). On imaging studies, m ultifocal
bone involveme nt is absent (582,1 667) .
Two types o f S P B have been defined:
one with no bone marrow i nvolveme nt
and the other with mini mal involveme nt
(< 1 0% clonal plasma cells i n the bone
marrow) (992 ,1 803 ,1 950). A solitary
often suffic ient to stimu late bleed i ng an d
facil itate osteo genes is. S ponta n eous he al­
ing has been reporte d . One quarter of so li­
tary SBCs recur. Cases of multiple lesio ns
have a higher recurr ence rate { 1 02 5). Lack
of bone formati on can usually be de mo n­
strated within the first year after treatment,
and reg ular follow-u p is recommend e d
{ 2038 ) . Curetta g e is not recomm en ded for
cases assoc iated with u ncomp lic ated ma­
ture florid osseou s dysplas ia, due to th e
likeliho od of i nducin g seques tration of the
hypovascula r mi neralized masse s.
Fe ldman A . L.
Ott G .
plasmacytoma with � 1 0% c l onal plasma
cells i n the bone m arrow q ualifies instead
as plasma cell myeloma.
H istopathology
The histopathological featu res are similar
to those of plasma cell myeloma. Typical­
ly, the plasma-cell nature of the tumour is
readily apparent , although for some poor­
ly differentiated (e. g . anaplastic) cases,
ies m ay be req u i re d to confirm li neage.
The i m m u nophenotype of SPB is also
similar to that of plasma cell myeloma.
l m m unohistochemist ry for the kappa
and lambda i m m unoglobuli n light chains
c an be helpfu l to s u p port plasma cell
clonal ity.
Progn osis and predictive factors
M ost patients achieve local control with
radiothe rapy. M edian overall survi val
i s about 1 0 years { 1 087). About 1 0% of
cases with no bone marrow i nvolvem ent
and 60% of cases with mi n imal i nvolve­
m ent p rogress to plasma cell myelom a
withi n 3 years { 1 950}. Adverse progn os­
tic factors include older age, lesio n size
> 5 cm, m onoclonal free light chains
in u ri ne , an abnormal serum free li ght­
chain ratio, and persistence of M protein
1 -2 years after d iagnosis {585,588,1 087,
1 426,2 429,2608) .