Ebook Surgical pathology of the head and neck (Vol 2 - 2/E): Part 2

17
Diseases of the Bones and joints
LeonBarnes
U/JiVel.Sity of fittSbt/rg/J School o f Medicine, and University oi Pittsburgh School o f Dental Medicine,
Pittsburgh, Pennsylvania

Robert S. Verbin* and Billy

N. Appel*

Unrversity of PittsOurgh School o i Dent,?/ Medic-ine, Pittshurgh, Pennsylva/~ia

1.

11.

Diseases of theJoints
1 x o r 1 Barws
A . Rheumatoid Arthrltis
B. Gout
C. CalciumPyrophosphateDihydrate
Crystal Deposition Disease (Chondrocalcinosis, Pseudogout)
D. Synovlal
Chondromatosis
E.Piglnented
Villonodular Synovitis
F. Ganglia-Synovial Cysts of the TemporomandibularJoint
Nonneoplastic Diseases of Bone and Joints
trrd

Ro1wr-t S. W h i t l ,

I 0.50
i050
I OS4

I OS7
I OS8
1061
1064
Lro,l

Brrrrws.

Hi/!\. N. AppcI

1066
1066
1077
1078
1079
1081
1084
1090
1005
1103

Osteomyelitls of the Jaws
Rolx)r/ S. K,r-hirr
Osteoradionecrosis
LCWIBt~r-ne.s

Relapsing Polychondritis
Lcorr Borne.s
D. Focal Osteoporotlc Bone Marrow Defect
Ro1wr-r S. V e r l h
E. CortlcalDefccts of the Mandible
Robrr-t .S. V w h i r ~
F. Paget's Disease o f Bone
Roherl L. feel
G. Fibrous Dysplas~a
Lrorl Htrrl~es
H.
Ccmento-Osseous
Dysplasias
Rohwr S. k r - l i n
1. Cherubism
Rilly N. A l p 4

A.
B.
C.

Ill. NeoplasticandNeoplastic-like Diseases of Bone
A . Solitary Hcmnngioma o f Bone
Leorr Barws
B.
Solitary
Lyrnphanglorna of Bone
Leorr Htrrrres
C. Angiomatosis of Bone
Leon Bnr-ms

D. Tori and Multiple
Exostoses
Robert .S. krl>irr
E. Exostosis:
Osteoma
Lro,l Btrnws
F. Osteochondrolna
Leor~Htrr-rres
"Retired.
1049

Leon Btrnzes

ntld

Rohc~r-t.S. Wrhirz

1109
I I09
1112
1112
1114
1116
1121


1050

Barnes et al.
G.

H.
I.
J.
K.
L.
M.
N.
0.
P.

Q.
R.
S.
T.
U.
V.
W.

Osteoid
Osteoma
Leorr Uorrre.s
Osteoblastoma
L c w H
~ trnles
Ossifymg
Fibroma
Rober-?S. Uvhiu
Chondroid(Cartilaginous) Metaplasia of the Larynx
Leotl Hrrme.s
Chondroma and Chondrosarcoma of the Larynx

I x o t l Ranzc..s
Chondroma and Chondrosarcoma of the Jaws and Craniofacial Bones
Chondrosarcoma of the Skull Base
Leon Rtrr-~re.~
Chondromyxotd
Fibroma
L c ~ r rRrrr-ties
Chondroblastoma
Leorr Brrr-rws
Chordoma
Lwrl Wrrrrw.s
Giant Cell
Tumor
Leon Rcrr-~(,s
Giant Cell
Granuloma
Roher-I S. Uvhirr
Aneurysmal Bone Cyst
Leorl Btrrnc.,s
Desmoplastic Fibroma
Leon Rarnc~.s
Fibrosarcornn
L w r ~Bnrrres
Osteosarcoma o f the Jaws, Skull. and Larynx
L c w Narrrc..s
Juxtacortical (Surface) Osteosarcoma
Leon B~rr-rres
Extraosseous
Osteosarcoma
Leon Uanrc~,s

Angmxcoma of Bone
LNNI B ~ I ~ I I P S
Ewing’s Sarcoma
Lcofr /hrr-~rc.s

X.
Y.
Z.
References

I. DISEASES OF THE JOINTS
I.A. Rheumatoid Arthritis
Introduction. Rheumatoid arthritis (RA) is a chronic
systemic disease characterized primarily by nonsuppurative. symmetrical inflammation o f peripheral synovial
joints. Extra-articular manifestations. however. are frequent and include various hematological, neurological,
cardiovascular, pulmonary, and cutaneous abnormalities.
Although the etiology is unknown, the disease is clearly
mediated immunologically (1,2). It occurs in all age
groups and affects about 2 5 3 % of the adult population.
It is more common in women and has an average age of
onset between 35 and 40 years (3).
ClinicalFeatures. There are many common anduncommon manifestations ofRA in the head and neck (4).
Among these are the following:

I. k ~ r w . r
Involvement of the larynx byRAisnot
unexpected because i t contains two paired diarthrodial, synovial-lined
joints: cricoarytenoid and cricothyroid (5-16; Fig. I and
2). Of the two, rheumatoid cricoarytenoid arthritis is the
more common and also themost disabling because this

joint is intimately involved in abducting and adducting
the true vocal cords.
The frequency with which the larynx is affected in RA
depends on the thoroughness of the examiner, the duration

Leorr Hrrr7w.s

112s
I l27
I130
1136
11.77
1142

I145
I l46
I14X
I 151
I156
I IS9
I l64
1 l69

l171
117.3
1178
11x1
11x2

I185

1186

and severity of disease, and whether clinical or autopsy
data are used. Results from various studies suggest that
26-78% of patients will manifest laryngeal symptoms
sometime during the course of their illness; 33-57% will
show physical evidence of disease onindirectand 7.5%
on direct laryngoscopy; 54-72% will exhibit abnormalities
on computed tomography (CT): and 45-100%will have
histological findings at autopsy (9-1 2,17).
In general, the more severe the disease and the longer
the duration, the more likely the patient will
have laryngeal signs and symptoms. In one series of 64 randomly
selected patients withRAof
9 years average duration
(range 9 months to 35 years). 17 (27%) hadlaryngeal
symptonls (9). In another study of 45 patients with RA of
13.9 years average duration (range 0.5-35 years) seen in
a university rheumatology clinic, 35 (78%) had one or
more laryngeal complaints ( 12).
Cricoarytenoid arthritis is usually bilateral and tends to
be not only more common. but also more severe in females
(7). Symptoms in descending order of frequency include a
sensation of a foreign body in the throat, hoarseness, fullness or tension in the throat, dyspnea. referred otalgia. odynophagia, stridor, dysphagia, and painful speech (7). Depending on whethcr the disease is in the acute or chronic
phase, physical tindings at laryngoscopy may be entirely
negative or may show a swollen, red mucosa; decrease
range of motion, fixation, or ankylosis of the joints; joint
deformities: or vocal cord immobility ( 5 ) . The correlation

yroid

1051

Diseases of the Bones and Joints

Cartilages of the Larynx

Hyoid bone
Epiglottic cartilage

Arytenoid cartilage
joint
Cricoarytenoid
Cricothyroid joint

Cricoid cartilage

between the extent of involvement of the cricoarytenoid
joint and symptomatology isnot reliable, for some patients
have shown severe joint disease
and had no symptoms,
whereas others have had no physical findings, but prominent symptoms (6,9). In general, patients who are symptomatic are more likely to have physical findings.
One of the most-feared complications of laryngeal RA
is ankylosis of thecricoarytenoidjoints
in astate of

Figure 1 Diagramshowing normalcartilagesand joints of the
larynx.

adduction.Thisresults
in significantnarrowing of the
glottis, and any superimposed upper respiratory infection,
no matter how trivial, may result in acute airway obstruction and the need for emergency tracheotomy.

2. TemporomandibularJoint
Of the patients with RA, 50-75% will have involvement
of thetemporomandibularjoint
(TMJ) (18-21). When

Figure 2 Cricoid (C); thyrold (T) joint: Note the joint space (JS)
and peripheral synovial lining (arrows).


Barnes et al.

1052

present, the joint involvement isusually bilateral, but
rarely occurs early i n the course of the disease. Signs and
symptoms, which are rarely handicapping or as severe as
in other joints, include morning stiffness, pain on movement of the jaws, difficulty in opening the mouth, referred
otalgia, crepitus, and swelling of the jaw. In more severe
diseases, one may see mandibular micronathia, with malocclusion secondary to destruction of the condylar head,
subluxation, and ankylosis. Juvenile rheumatoid arthritis.
on the other hand, may be more serious and interfere with
growth and development of the jaws.

In addition to the keratocol1.junctivitis sicca (dryeye)
component of Sjogren’s syndrome, RAmaymanifest in

the eye a s iritis. iridocyclitis, and scleritis. In mostinstances. these are late manifestations of the disease.

4.

Ecw

Hearing impairment in patients withRAis a subject of
controversy, and itsnature and extent hasnotbeen fully
delineated (22-28). Since the incudomalleal and incudostapedial articulations are synovial joints with cartilaginous articular disks. one would assume thattheywould
be subjected to the same ravages of RA as seen in small
joints elsewhere i n the body (37). Surprisingly, there have
beenvery few histological studies ofthe temporal bone
in patients with RA. In those five instances in which the
ossicles have been evaluated, the histological findings
have been normal or equivocal at m o s t ( 2 3 3 ) .
Sensorineural hearing loss is one of the m o s t common
auditory abnormalities i n RA. I t occurs i n 2648% of
patients andis presumably due to neuritis or vasculitis.
or both, of the auditory nerve or cochlea (27-30). There
is no relation between hearing loss and duration or activity
of RA; but, according t o Goodwill et a l . patients with
rheumatoid nodules are more likcly to experience sensorineural deafness (23).
Although patients with RA frequently manifest an increased “stiffness” of the ossicles on specialized testing,
clinically significant conductive hearing loss isunusual
(28). Some drugs used in the treatment of RA, especially
salicylates, are potentially ototoxic and may also contribute to hearing abnormalities.
S.

Nose.

In rare instances, patients with RA may experience spontaneous perforation ofthenasal septum (31,32). Although
presumably caused by vasculitis or local vasospasm, biop-

sies from the edges of these ulcers havenot
evidence of vascular damage.

shown

6. S u l i ~ ~ r rGlands:
y
Sjogrer? ‘ S Syclrotw

Fifteen to 2.5% of patients with RA may manifest Sjogren’s syndrome, an idiopathic immunologically mediated, inflammatory-destructive disorder of thelacrimal
and salivary glands, leading to dry eyes and mouth. This
syndrome is discussed i n greater detail i n Chapter 13.
7. Lymph No&.s
Lymphadenopathy, either regional or generalized, is not
uncommon in patients with RA and is thought to be related
to the immune response associated withthe disease. In
some instances. the lymph nodes are actively involved in
the production of rheumatoid factor.
Pathologists should be aware that patients with RA who
are treated with a combination of methotrexate and prednisone may develop an Epstein-Barr virus lymphoid proliferation that
may
easily he mistaken for malignant
lymphoma (33-35). Ifrecognized, reduction or cessation of
immunotherapy will result in regression of the adenopathy.
X.

Rhcwrtrtrtoid N o c l ~ r l t ~ s

Rheumatoid nodules develop in 25% of patients with RA
and are associated with active disease. high titersof
rheumatoid factor, vasculitis, and a poor prognosis (3,36).
They are frequently located over extensor surfaces, bony
prominences, and other pressure areas, and occur within
the dermis. subcutaneous tissue, or periosteum. They may
also involve the synoviurn. bone. dura. eye, and various
internal organs, including the heart and lungs (37).
Involvement of the larynx is distinctly unusual, but when
it occurs. thetrue
vocal cords appear to bethemost
frequent site ( 3 8 4 1 ; Fig. 3). They have also been described in the false vocal cords. epiglottis and the mucosa
and muscle adjacent to the cricoarytenoid joint (9,40).
The nodules are soft and pale gray toyellow-white.
Rarely. they may ulcerate.
9.

Vtr.scx1iti.s

Ten to fifteen percent of patients with RA will develop a
vasculitis, either digital or systemic. When systemic, it
maybe impossible to separate from polyarteritis nodosa
on histological examination alone. Vasculitis is usually
associated with rheumatoid nodules and high titersof
rheumatoid factor. I t is thought t o be the result of immune
complexes and usually manifests as cutaneous-mucosal
ulcers or a neuropathy (3,10,42.43).

1053

Diseases of the Bones and Joints

Figure 3 This 66-year-oldcoalminer,
with a 12-year hlstory of rheumatold arthritis, died of respiratory failure secondarytoanthracosilicosis
and pulmonary
fibrosis. An autopsyrevealedbilateral
rheumatoid involvement of the cricoarytenoid joints and rheumatoid nodules In
thesofttissue
of theglottisandsubglottis. The glottic nodules are illustrated.
Thyroid cartilage containingmarrow is
present in the lower left hand comer (heX50).
matoxylin
and
eosin
[H&E]
(Courtesy of G Perkins,Universityof
Westem Ontario, London, Ontano and R
Kessler, Montefiore Hospital, Pittsburgh,
PA.)

10. Neuropathy

12. Amyloid

Amyloid may develop in up to 20% of patients with RA.
The complication of neuropathy, whichmay be sensory or
This subject is discussed in greater detail in Chapter 30.
motor, occurs in about 10% of patients with RA. In some

instances, this is related to a small vessel angiitis involving Pathology. The pathology is identicalwiththatobserved in peripheral joints. Early in the course of the disthe nutrient blood vessels (vaso nervorum) of nerves, reease, the synoviumis congested, edematous, hyperplastic,
sulting in demyelination or even frank necrosis. A compressive (entrapment) neuropathy accounts for most
of the
and extensively infiltrated with plasma cells and lymphocytes. As the abnormal synovium (pannus) enlarges, it exremaining cases, suchas in the carpel tunnel syndrome.
tends over the articular surfaceand destroys the cartilage,
Involvement of the cervical spine is recognizedto be a
common manifestation of RA and typically appears latein
predisposing the joint to the ravages
of secondary degenerative joint disease. As the disease progresses, the pannus
the course of the disease (44,45). Although about 25% of
may become fibroticor even ossify, resultingin a “frozen”
patients will exhibit radiographic abnormalities
of the cerjoint.
vical vertebrae (usually varying degrees of subluxation),
only a fewwill ever develop neurological symptoms
(44).
Rheumatoid nodules are composedof a central zoneof
fibrinoidnecrosis
and aperipheralborderconsisting
11. MyopathyandMyositis
of palisading histiocytes, mononuclear inflammatory cells,
and fibroblasts (Fig.3 and 4). Occasionally, multinucleated
Muscle atrophy in RA may be due to disuse or ischemic
giant cells may be observed and, in this instance, thenodneuritis-vasculitis (as noted earlier). The latter often reules may be confusedwith caseating granulomas.
sults in focal or diffusedemyelination with subsequent
Treatment. In general, medical treatment of the sysneurogenic atrophy.
temicdiseasewillalleviate
or ameliorate many of the
One may also see nodular collections of chronic inhead and neckmanifestations.Some
of theproblems,

flammatorycells,principallylymphocytes,lyingwithin
however, may havetobeapproachedsurgically.
Some
the muscle, which may also contribute to muscle weakpatients with severe cricoarytenoid arthritis may experiness. In contrast with dermatomyositis, these inflammaence ankylosis of the joint(s) with fixation of the vocal
toryfociare
not associated with regenerativemuscle
cords in a state of adduction and significant airway comchanges or necrosis.
promise. In these instances, arytenoidectomy with vocal


Barnes et al.

1054

Figure 4 Rheumatoidnodule composed
of acentral zone of fibrinoid necrosis
of histiocytes,
andapenpheralborder
fibroblasts and inflammatory cells (H&E,
X 140).

cord lateralization will ensure a safe airway and preserve
by hyperuricemia and recurrent violent attacks of arthritis
patient’s
voicethe
(13).
intra-articular
secondary
to
accumulation

of monosodium
urate crystals.As the disease progresses, the joints become
I.B. Gout
become deposits urate
and deformed,
progressively
grosslyvisibleastophi(Figure
5). Thediseaseisnot
Introduction. Gout, which may be primary or secuncommon, for about 5% of patients in major arthritis
ondary, is a disorder of purine metabolism characterized
clinics are estimated to have gout (1).
~~

d
Figure 5 Goutytophusonthehelix
of theear(arrow).(Courtesy
RE Lee,
Unwersity of PittsburghMedicalCenter, Pittsburgh, PA.)

. . ..


1055

Diseases of the Hones and Joints

In humans, wholackthe
enzyme uricase, the major
end product of purine metabolism is uric acid. In a normal
healthy individual, about 700 mg of uric acid are turned

over each day. About two-thirds o f this is excreted i n
the urine, and the remainder is eliminated through the
gastrointestinal tract, where it is further degraded by
colonic bacteria ( I ) . Therefore hyperuricemia results when
there is either an overproduction of purines or faulty
excretion, or a combination thereof.
Prirrwry g o u t
Primary gout accounts for 90-9S% of all cases and is the
term usedto describe those individuals whosc hyperuricemia is due to an “inborn genetically determined metabolic defect leading to a pathologic de novo biosynthesis
and/or retentionofuric
acid” (2). Ofthis group. about
90% are men:when i t occurs in women, mostarepostmenopausal. The peak age of onset is the fifth decade.
Twenty-five percent o f the relatives of patients with gout
have asymptomatic hyperuricemia ( I ).
The severity and rate of progression of gouty arthritis
are extremely variable. The following four phases of the
disease are recognized.
l.

A.s!‘rrll,torlltrtic’
Hyperuricewritr

Overall. about 1 5%-3S% of individuals with sustained
hyperuricemia will develop gout. The incidence, though.
varies withthe duration and degree of elevation ofthe
serum uric acid level. For example, if an individual maintains a serum level o f C) mg% or nlore for 14 years, he or
she has an 83%: chance of developing gout ( I ,2).
2.

AcrIIcJ C ‘ o r r l ~Arthritis

The initialattack is typically monoarticular and involves
a peripheral joint. usually the great toe (podagra) i n SO7 S % of the cases. but occasionally the ankle, wrist, heel,
or kncc. The onset is sudden, reaches a maximum intensity
i n a few hours, andwill resolve spontaneously i n a few
days to weeks if left untreated. Such attacks maybe
precipitated by prolonged fasting, excessive alcohol consumption. surgery. joint trauma. or ingestion of drugs that
intcrfcre withrenal
excretion of uricacid
(especially
thiazides).
3.

lr1tvrcriticwl (lrl/c~r\wl)
Golrl

Intercriticalgoutis
the asymptomatic period between
acute attacks. I t mayvaryfrom
weeks to years. but
most individuals will suffer another acute attack within 6
months t o 2 years after theinitial attack. As the disease
progresses, the attacks become more frequent and scverc,
and multiple joints may become involved.

4.

Chronic Topkcrceous Gout

Gross deposits of monosodium urate crystals are referred

to as tophi (from the Greek meaning “chalk stone”).
Before the advent of effective drug therapy, 50-60% of
patients developed tophi; nowadays, the incidence is 1335% ( l ) . Their development is related to the length of the
disease, degree of elevation ofthe serum uric acid, and
the severity of renal involvement ( I ) .
In general, patients have had gouty arthritis for an average of 1 0 years before tophi begin t o appear ( 2 ) . Thcy arc
rarely observed at the time of the first attack. Themost frequent sites are the synovium, subchondral bone, olecranon
bursa, Achilles tendon. subcutaneous tissue of the forearm
near the elbow. and thc helix of the ear (see Fig. S). They
are nonpainful, firm, and salmon pink
when
viewed
through the skin. Occasionally, the skin will ulcerate and
drain white chalky material. Large tophi may interfere with
joint function, and some will erode bone and cartilage and
produce secondary degenerative joint disease.
Patients with gout also have a higher incidence oidiabetes mellitus, obesity, atherosclerosis, hypertension, and cardiovascular disease. In 2040%. of cases, uric acid stones
will develop and occasionally result in pyelonephritis ( 1.3).
Kidney disease is the single most important cause of death
in gout (3).
Seco,1cltrry go111

Secondary gout accounts for the remaining S-lO%. of
cases and represents a complication of some otheracquircd disease in which there is accelerated nucleic acid
turnover or impaired excretion of uric acid. Hcmatological malignancies. hypertensive cardiovascular disease.
and chronic renal disease are some of the more common
causes. I n the secondary form. there is no hereditary tendency. scrum uric acid levels are higher, the age of onset
may be younger, and there is a higher incidence in women.
The pathogenesis ofthe acute attack of gout is complex. As the urate crystals begin to nccumulate within the
joints, they are immediately phagocytosed by neutrophils

which, i n turn. liberate lysosomal enzymes thathave ;I
destructive effect on articular cartilage. In addition. the
urate crystals activate Hagemm factor which stimulates
cytokine production, resulting i n increased vascular permeability and a greater concentration of neutrophils. The
ensuing anaerobic metabolism lowers the pH. which further promotes uric acid production. Thus. a vicious cycle
is cstablished.
5. Hetrd

trtd

N d Mtrr1i~sttrtiorl.s

Although gout may affect the head and necki n any stage of
the disease, it generally occurs only in patients with long-


Barnes et al.

1056

crystals and changes of secondary degenerative joint disstanding disease.Tophi and cricoarytenoid arthritis are the
prime manifestations(4-10). In this region, tophi are most eases.
Differential Diagnosis. The differential diagnosis inoften observed on thehelix of the ear or in the vicinity of
cludes Teflon granuloma and pseudogout.Patientswho
the true and false vocal cords; however, they been
have dehave unilateral vocal cord paralysis are often treated
by
scribed in thesoftpalate,uvula,glossoepiglotticfold,
tongue, hyoid bone, thyroid cartilage, epiglottis, subglottis,injecting the paralyzed cord with Teflon, which expands
the cord and, thereby, improves speech

and lessens the
tracheal cartilage, first part of the esophagus, sclera, condifficulty with secretions. Teflon particles vary from round
junctiva, and hypopharynx (5,6,8,10; seeFig. 5 ) .
toovoid and tendtohaveaclearcenter
and athick
Involvement of thecricoarytenoidjointresultsin
border. They also elicit a foreign body giant cell reaction
hoarseness, dysphagia, dysphonia, pain,and possible joint
and fibrosis and will polarize, which may result in confufixation, with aspiration pneumonia.As might be expected,
sion with gout (see Chapter 5 ; Figs. 18 and 19). Sodium
hoarseness is the chief symptom when tophi involve the
urate crystals, however, are thinand elongated, not round
true vocal cords. Aural tophi can be confused clinically
or ovoid. In addition, the clinical history, normal serum
with chondrodermatitis nodularis. The presence of pain,
uricacidlevel, and negativeDeGalanthastainforuric
however,favorsthe
latter. Goutyinvolvement of the
acid readily allow one to distinguish a Teflon granuloma
temporomandibular joint is very rare.
from gout.
Pathology. Tophi arecomposed
of aggregates of
Pseudogout or chondrocalcinosis may also be confused
elongatedneedle-shaped,cleartolightbrowncrystals,
with gout. In this disease, calcium pyrophosphate dihyoften appearing as “bundles of wheat.” The crystals, in
drate crystals are deposited in soft tissues or joints (14).
turn, are immediately surrounded by foreign body giant
The pyrophosphate crystals appear as short, blunt rods,
cells,histiocytes, and densefibrousconnectivetissue

rhomboids, or cuboids that are weakly birefringent under
(3,ll-13; Fig. 6 ) . Thecrystalsshownegativebirefrinpolarized light (Fig. 7).
gence. When a primary color compensator
is positioned
Treatment
and
Prognosis. Treatment
consists
of
betweentwopolarizinglenses,thecrystals
will change
drugs, such as colchicine, allopurinol, probenecid, corticofrom yellow to blue on rotation of the polarizing lenses
steroids, and nonsteroidal,anti-inflammatoryagentsdefrom parallel to perpendicular.
signed to intermpt the afore noted cycle
of events or to
When gout involves a joint, it
may produce a gross
deformity, with prominent intra-articular deposits of urate lower the serum urate level(15). If the gout is secondary,

Figure 6 Gouty tophus composed of needle-shaped urate crystals
have evoked a forelgn body giant cell reactlon (H&E, X 350).

that


nes

Diseases of the

and Joints

1057

Figure 7 Crystals of calciumpyrophosphatedihydrate(pseudogout)appear in tissue as rhomboids, cubes, or
rectangles. Note the multinucleated giant cells (H&E, X400). Compare with
Fig. 6.

then control of the primary disease is mandatory. Tophi
may dissolve with medication,butlargeronesthatare
disfiguring or that interfere with joint function may have
tobesurgicallyexcised.Jointsseverelydeformed
by
secondarydegenerativejointdiseasefrequentlyrequire
arthroplastic procedures. Although the purine content of
daily food consumption does not substantially contribute
to the serum urate concentration; nevertheless, moderation
in dietary purine consumption is indicated (15).
With the advent of effective antihyperuricemictherapy,
the natural history of the disease has been altered. Nowadays, only a few patients develop tophi, disabling joint
problems, or life-threatening renal disease.

I.C. Calcium Pyrophosphate Dihydrate Crystal
Deposition Disease (Chondrocalcinosis,
Pseudogout)
Introduction. Zitnan and Stag and McCartyetal.
wereamongthe first torecognize and characterizethe
condition now known as calcium pyrophosphate dihydrate
(CPPD) crystaldepositiondisease(chondrocalcinosis,
pseudogout, CPPD arthropathy: 1-4). In this disorder, for
reasonsunknown,crystals

of CPPDaccumulateinthe
joints,especiallytheknee,wrist,metacarpophalangeal,
hip and spine, and occasionally, the para-articular tissues
of older persons.
The disease is not uncommon. It hasbeenobserved
in the knee joint, for instance, either at autopsy
or by
radiographic examination, in 2.2-34% of patients older
than 60 years of age ( 5 ) . It is more common in men by a

ratio of 1.51 and occurs in patients averaging 72 years
of age (5).
Although most cases of CPPD disease are idiopathic
and sporadic, a few are hereditary and are transmitted as
an autosomal dominant trait, whereas others are precipitated by trauma or surgicalprocedures.About10%
of
cases are associated with a variety of metabolic disorders,
especially hyperparathyroidism, hemochromatosis, hypothyroidism,
gout,
amyloidosis,
Wilson's
disease,
and
ochronosis (5,6).
CPPD disease ranges from totally innocuous to incapacitating, and is often mistaken clinically for a variety
of
musculoskeletal disorders. Ryan and McCarty recognize
several variants of the disease, which they designate as
type A through type F (5). In type A (pseudogout), the
diseasepresents as an acute, self-limited, monoarticular

arthritis that involves the knee in over 50% of the cases
and is often confused with gout. Type B (pseudorheumatoid arthritis) is characterized by multiple joint involvement, with subacute attacks lasting from weeks to several
months.Thisvariant
may bemistaken for rheumatoid
arthritis. About 10% of patients with this type will also
have positive tests for rheumatoid factor, but only in low
titers. q p e s C and D (pseudo-osteoarthritis) involve the
largejointsbilaterallyand,accordingly,arefrequently
misdiagnosed as osteoarthritis. Patients who give a history
of superimposed acute joint symptoms are labeled astype
C, whereasthosewhodo
not have an inflammatory
component are designated as type D. Type E (asymptomatic),asthenameimplies,refers
to thoseindividuals
whohaveonlyradiologicevidence
of disease,butno


Barnes et al.

1058

symptoms. This variant may be the most frequent of all.
T
\
p
e F (pseudoncuropathic joint) istherarest
and most
severe form. It resembles Charcot joint, but yet with few
exceptions, these individuals do not have an underlying

neurological abnormality.
Patients with CPPD disease have normal levels of
serum calcium, phosphorus. and uric acid. Theonly exceptions are those instances whenthe disorder may coexist
with hyperparathyroidisti1 or gout.
As i n gout, the crystals may incite an inflammatory
reaction that results in a cascade o f events that ultimately
lead to joint destruction.
1.

H c w l a r d Nock

Mtrrli~~frsttr1iorl.s

Rarely, CPPD disease involves theheadand
neck, and
when it does, the temporolnandibular joint (TMJ) is the
most likely site (7-14). The disease in this area is typically
unilateral. occurs in patients between SO and 60 years of
age, and manifests as a prealtricular swelling or discrete
tnass that is often mistaken
clinically for a tumor of thc
parotid gland or external auditory canal.Some patients
have complained of tenderness or pain, often referred to
thcear. and a “clicking” sensation on opening the jaws.
Deviation of the mmdible, difficulty on opening the
mouth. and decrease i n hearing, although described. are
unusual (9- 12).
Radiography. I n the knee, two of’ the earliest and
most characteristic features of CPPD disease arc the prcsence o f linear. punctuate calcitication o f the menisci and
calcitic deposits in the midzone of the hyaline articular

cartilage. I n the TMJ. thetypical appearance isthat o f
either a slightly or heavilycalcified intra-articular mass.
with or without erosion of thc subjacent cartilage and bone
( I O . 13). The calcification tends to be fluffy or granular.
Pathology. TheCPPD crystals appear in tissue sections as slightly basophilic rhomboids, cubes or rectangles
and, only rarely, as needles (IS-17; Fig. 7). In general.
needles. if seenat a l l . tendto occur in acute disease.
whereas the other forms arc seen i n both acute and chronic
conditions. The crystals may lic free in the tissue without
evidence of an inflammatory response. or they may evoke
acute and chronic inllammation. with eventual multinucleated giant cell reaction and fibrosis.
Tophi similar to those seen in goutmay also occur
(tophaceous pseudogout). However, in contrast with gout,
the tophi of CPPD disease occur only i n the vicinity o f
the diseased joint and are never widely dispersed.
Differential Diagnosis. CPPD disease must be distinguished from gout. This canltsually be nccomplished
by obtaining a serum uric acid level and on viewing the
crystals by both light and polarized microscopy (see Figs.

6 and 7). More sophisticated tests. such as X-ray diffraction and infrared spectroscopy, can also be used. Table I
liststhe features that are useful in separating the two
conditions.
Treatment and Prognosis. Patients with limited,
asymptomatic disease generally require no treatment. Others. however.may require ( a ) joint aspiration to remove
the crystals. (h) colchicine or nonsteroidal anti-intlammatory agents, (c) local injections of steroids, or even (d)
joint immobilization. Those with more severe joint diseasc
may even require arthroplastic surgery. Interestingly, when
CPPD disease is associated with other metabolic diseases
(hyperparathyroidism,hypothyroidism. and such), corrcction of the underlying metabolic disorder has not resulted
i n the disappearance of crystallinc deposits (S).

I.D. SynovialChondromatosis

Introduction. Synovial chondrotnatosis (SC) is a benign condition characterized by the occurrence of metaplastic cnrtilaginous or osteocartilaginous nodules within
the synovial membrane of joints and, occasionally, of
bursae and tendon sheaths. As the disease progresses, the
nodules may become detached to form intra-articular loose
bodies. Two forms o f the disease are recognized: primary
and secondary ( I ).
Pritnary synovial chondromatosis (PSC) is uncotntnon.
In this form of the disease, the metaplastic nodules appear
de novo. with no evidence of an underlying predisposing
joint disorder. The etiology is unknown. but ;I benign
neoplasm or a response to chronic, repetitive. low-grade
trauma have been proposed ( I,?).

Compohition
Shape

Sodium 11rate

Calcium pyro-


1059

Diseases of the Bones and Joints

Primary SC occurs in all age groups (average 40-45
years) and is twoto three times more common in males
(35). The knee is,by far, themost common location, accounting for70% of all cases,with the second most common location being about equally divided between the hipel-and

bow (43). The shoulder,
wrist,
metacarpal,
and
temporomandibular joints are rarely involved.
The disease
is monoarticular and unilateral in 90% of patients (5).
Secondarysynovialchondromatosis is commonand,
as the name implies, is always secondary to some other
condition, such as osteochondritis dessicans and the various inflammatory and noninflammatory arthropathies.
The
knee and hip are the preferred sites.
1.

Temporomandibular Joint

Synovial chondromatosis rarely involves
the temporomandibular joint (TMJ) (2,6-25) (Figure 8). As of 1989, only
47 cases were recorded in the literature (6). The disease
more often involves the right T M J (6045% of all cases)
than theleft and, in contrast with other sites, affects
women
(5747% of all cases) more than men (6,9,13). The mean
age at diagnosis is 47 years (range
18-75 years; 6).

Signs and symptoms include the presence
of a preauricularmass or swelling,attimesassociatedwithpain,
crepitus,clickingsensation on opening the mouth, restrictedmovement of thejaws, and deviation of the
mandible to the side of the lesion on opening the mouth.

As such, the disease is often mistaken
for a parotid tumor.
Radiography. Radiographicprocedures may reveal
the presence of intra-articular loose bodies, widening or
narrowing of the joint space. deformity of the condylar
head, and erosion of bone (13,15,18; Fig. 9). In 2540%
of patients,plainradiographs will benormal (9,11,1416). Theabsence of radiopaquebodies on radiologic
examination does not exclude the diagnosis because the
appearance of loosebodiesvaries
with thedegree of
calcification of thecartilaginousnodules.
In these instances,computedtomography(CT)
or magneticresonance imaging (MRI) may be helpful.
Pathology. Miligramrecognizesthreephases of the
disease: (a) active synovial disease without loose bodies;
(b) synovial nodules associatedwith loose bodies; and (c)
multiple loose bodies,with inactive synovial disease (26).
On gross inspection, the synovial membrane
may be
either focally or diffusely involved, with nodules ranging

Figure 8 Synovlal chondromatosls Involving the left temporomandibular joint of a 67-year-old woman. The disease was so extenslve
that the head of the condyle had to be resected. Note the confluent
nodules of cartilage covenng the artlcular surface.


1060

Barnes et al.

Figure 9 Specimenradiograph of Fig. 8 showing pressure erosion
of the underlying bone by synovial chondromatosls.

frommicroscopictoseveralcentimeters(seeFig.
8).
The disease begins with the formation of round discrete
cartilaginousislands within thesubsynovialconnective
tissue, rather than the synovial cells per se (Fig. 10). The
chondrocytes are plump, hyperchromatic, and occasionally binucleated.As the nodules enlarge,they may undergo
patchy calcification or ossification,losetheirsynovial
attachment, and float free in the joint space, where they
continue to enlarge, nourished by the synovial fluid (27).
According to Forssell et al., the loose bodies are found
mostly in the upper TMJ joint space and only in a few
cases in the lower joint compartment (15). In the TMJ,
thenumber of loosebodieshasrangedfrom
1 to 480,
with most cases containing between 15 and 50 (15).
In rare instances, synovial chondromatosismay simultaneously coexist with other joint diseases, such as pigmented villonodular synovitis and pseudogout (28,29).
Differential Diagnosis. Caution must be exercised in
evaluating biopsy specimensof synovial chondromatosis,
because the histological changes,on occasions, are similar
enough to those of chondrosarcoma that they may cause
diagnosticconfusion,especially in thosefewinstances

forwhichthediseaseextendsbeyondthejointspace
(11,17,19,22).
If the disease is clinically and pathologically confined
to the synoviumand joint space, ratherthan bone, then the
cytological atypia can usually be ignored. Primary chondrosarcomas of the synovium and chondrosarcomas allegedly arising from preexisting synovial chondromatosis are

exceptionally rare, but have been described(30-32). Several histological features should suggest malignancy. The
most important ones are (a) the loss of a nodular growth
pattern, with spindling of the cells at the periphery of the
chondroid nodules; (b) myxoid change in the matrix; (c)
hypercellularity; (d) necrosis; and (e) invasion
of the adjacent bone, ratherthan pressure erosion(30).
Synovial chondromatosis may also extend beyond the
TMJ into the parotid gland and masquerade, on biopsy,
asa pleomorphicadenoma (IO). The presence of an
epithelial component, as seen in a pleomorphic adenoma,
readily allows one to distinguish between these two entities.
Treatmentand Prognosis. Because there is no tendency for the disease to resolve spontaneously, treatment


es

Diseases of the

1061

Figure 10 Low-power magnification
of synovialchondromatosisshowmg
well-circumscribed nodules of focally
calcified cartilage lying in the subsynovial connective tissue (H&E, X40).

consists of surgical removal of theloosebodies
and
excising as much of the synovial membrane as possible
(4). Failure to treat can result in secondary degenerative
jointdisease. For moreextensivedisease,it

may be
necessary to resect the condyle and reconstruct the joint.
More recently, there have been attempts to remove the
diseasedsynovium and loosebodiesarthroscopically,a
relativelynoninvasivealternativetoopenarthrotomy
(2,24). However, if the loose bodies are large, they may
not be able to be removed through an arthroscope. Radiotherapy
.. is of no use (4). Local recurrences are infrequent
and are related to the adequacy of the synovectomy.
In rareinstances,synovialchondromatosis
may be
locallyaggressive.Therearerarereports
of thedisease
extending beyond the TMJ to involve the parotid gland,
external auditory canal, and even the middle cranial fossa
(10,11,17.19,22).

the fingers-so-called giant cell tumor of tendon sheath
(localized PVNS, nodular tenosynovitis; 2-4).
Diffuse PVNS, with few exceptions, is limited to the
articular synovium. In contrast with localized PVNS, it
presents as a diffuse thickening
of the synovial membrane.
Although a few instances of multiple joint involvement
have been recorded, it is essentially a monoarticular disease. The knee and hip are the most common locations,
accounting for70 and 16% respectively, of all cases (2,5).
The ankle, foot, wrist,
elbow, and shoulder constitute most
of the remaining sites.

Clinical Features
I.

Difbse PVNS

Reports of diffuse PVNS occurring
in the temporomandibular joint (TMJ) are extremely rare(6-13). Youssef et al.
reported an example in 1996 and reviewed 16 additional
cases in the literature (1 3). These 17 cases occurred in 5
I.E. Pigmented Villonodular Synovitis
males and 12 females who ranged in age from 10 to 62
years (average 44 years). The left TMJ was the site of
Terminology. Pigmented
villonodular
synovitis
(PVNS) is an idiopathic, benign, sometimes locally aggres- disease in 13 cases and the right in 4.
In this area, the disease usually presents as a gradually
sive inflammatory-proliferative synovial disorder that
was
enlarging,preauricularswelling,occasionallyassociated
first recognized in the 1850s. However, it was Jaffe et al.,
with pain on mastication. The joint eventually becomes
in 1941, whofirst introduced the term PVNS
and defined it
“stiff” andmay limit opening of the oral cavity. Some
as a clinicopathological entity
(1). The disease exists
in two
patientshaveevenexperiencedconductivehearingloss
forms: localized and diffuse, with the former accounting

and serousotitismedia,presumablyfrominterference
for about 75%of all cases and the latter 25% (2).
with the function of the eustachian tube (10).
The localized variant generally presents as a discrete
On physical examination, the joint
may appear swollen
mass with a smooth border. Although it may involve the
(owing to synovial thickeningand effusion) and, attimes.
joint space (localized nodular synovitis), most are extrawarm, but not necessarilytender. In other cases, a discrete,
articular, with 75-80% arisingfromtenosynovium
of


1062

firm,nonmobilemass may bedetected,whichisoften
mistaken for a parotid tumor.

2. Localized PVNS
At least two cases of localized PVNS of the T M J have
been described. One occurred in a 36-year-old man, who
presented with rightconductive-hearinglossassociated
with a fixed mass and serous otitis media. At the time of
surgery, it was found to extend beyond the joint space
into the adjacent tissue (14). The other case involved a
55-year-old woman, with a left TMJ mass associated with
pain and difficulty in opening her mouth (15).
Radiography. Radiographicstudies show aconstellation of findings that may include one or more of the
following:(a)a
normal or narrowed jointspace,(b)

diffusethickening of thejointcapsule,(c)alocalized
intra-articular or para-articular soft-tissue density, withor
withouterosion of theadjacentarticularcartilageand
bone, and (d) oneor more well-circumscribed intraosseous
cysts presumably partly owing to PVNS spreading along
nutrient vessels into the interior bone (2,5,16,17; Fig.11).
Pathology. On gross examinationthesynoviumexhibits various shadesof brown, dependingon the hemosiderin content, and is diffusely thickened, shaggy and villiform, or nodular. Microscopically,elongatedpapillary
fronds are capped by hyperplastic synovial cells (Fig. 12
and 13). The stroma is vascularized
and varies from cellular to collagenous;with areas between these two extremes.
The cellular areas are composedof histiocytes (?synovial

Figure 11 An MRI of pigmentedvillonodularsynovitrs of
the left temporomandibular jolnt in a 60-year-old man presenting as a low signal intensity leslon (white “X”). Compare
with the normal joint on the right. (Courtesy of J Weissman,

Universlty of Pittsburgh Medical Center, Pittsburgh. PA.)

Barnes et al.

cells), foam cells, multinucleated giant cells,
and admixed
neutrophils and mononuclear inflammatory cells (Fig.14).
Hemosiderin may be found within the cytoplasmof synovial cells and histiocytes or lying free within the stroma.
Villi frequently fuse to form nodules, but if the fusion is
incomplete, elongated slitsor cavities are formed (see Fig.
13). A few cases have also shown features
of coexistent synovial chondromatosis (18,19).
With the exceptionof villi,
localized PVNS shows identical changes.

PVNS may also be diagnosedby fine-needle aspiration,
provided the cytopathologist is provided with sufficient
clinical information (20).
Differential Diagnosis. The two lesions that aremost
often confused with PVNS are malignant fibrous histiocytoma(MFH) and thecentral(intraosseous)giantcell
granuloma (CGCG). In contrast with MFH, PVNS usually
does not exhibitadiffusestoriformpattern,significant
pleomorphism, abnormal mitoses, or prominent necrosis.
MFH also lacks villi. In turn, CGCG is contained within
bone and rarely extends beyond its osseous boundaries,
whereas PVNS of the TMJ is primarily (but not always)
an intra-articular disorder.
Treatmentand
Prognosis. Treatmentconsists of
completeremoval, which generallyrequiresasynovectomy (2). If the adjacent boneis involved, simple curettage
is usually sufficient, but if extensive, local resection with
joint replacement may be necessary. Although synovectomy removes the disease, some patientsmay end up with
a less functional joint and greater
pain than before the operation (2). Radiation therapy has also been used and may


Joints
Diseases of the Bones and

1063

Figure 12 Pigmented
villonodular
synovitw:
Low-power

view showing
elongated papillary fronds of synovium
(H&E, X 100).

cause regression of the disease, but joint stiffness is a frequentcomplication. In addition,thelong-termcarcinogenic potentialof such therapymust also be considered.
At least 2of the 17 (12%) casesof diffuse PVNS of the
TMJ reviewedby Youssef et al. developed oneor more localrecurrencesfollowingattemptsatsurgicalexcision
(13). This compares withan average rate of recurrence of
22% (range 1746%) when all joints are considered (2).
Although usually confined to the joint space or immediate para-articular area, diffusePVNS may be locally ag-

gressive. Eisig et al. have reported a case that extended
to the middle cranial fossa and near the carotid canal into
the external and middle ear and infratemporal fossa (10).
Suchcasesarefortunatelyrare
and do not necessarily
indicate malignant transformation.
Etiology. The etiology of PVNS has been debated
foryears and stillcontinues.Thecontroversycenters
aroundwhetherthelesionisreactive,inflammatory,
or
neoplastic. Some believe that PVNS is related to trauma.
This theory is diluted somewhat by the fact that only38%

Figure 13 Pigmented
villonodular
synovitis: Low-powervlew showing fusion of thepapillaryfrondscreatinga
nodule (H&E, X 100).

1064

Barnes et

villonodular
Figure 14 Pigmented
synovitls: Higher power showlng histiocytes (?synovial cells) wlth hemoslderin. foam cells, inflammatorycells,
multlnucleated glant cells and focal fibrosls (H&E. X200).

of patientscanrecalla
history of trauma (2). Whether
chronic, repetitive unperceived, minor trauma is a factor,
however, remains uncertain.
Immunohistochemical studieshave provided mixed results.Someindicate
that theproliferatingmononuclear
cells are of monocyte-histiocyte derivation, whereas others suggest that they are of synovial origin (21-23). Ray
et al. have identified a clonal abnormality (trisomy 7) in
a single caseof PVNS, which supports the contention that

15 Collapsed
multilocular
ganglion of the right temporomandibular jointmasqueradingas
a parotld
tumor.

Figure

the lesion is a neoplasm (24). It is entirely conceivable
from the foregoing studiesthat the etiologyof PVNS may
be multifactorial and is not related to a single event.

I.F. Ganglia-Synovial Cysts of the
Temporomandibular Joint
Terminology,Etiology,andPathology.
Theterms
ganglion and synovial cyst are often used interchangeably


Diseases of the Bones and Joints

1065

Figure 16 Ganglion of temporomandibularJolnt shown in Fig. 15: Note
that it is lined by only connective tissue,
not epithelium; therefore, it is
a pseudocyst
and
not
a true cyst (H&E,
x 200).

and are erroneously considered bymany to be synonymous. Althoughboth occur near joints,
they differ in origin
and histology. Ganglia arise as a resultof idiopathic myxoid degeneration of para-articular connective tissue(1). As
the thick. tenacious,gray-white ground substance accumulates, unilocular or multilocular
1- to 4-cm cysts are formed
(Fig. 15). The cysts are lined only
by dense connectivetissue, ratherthan synovium (Fig. 16). Consequently,
they are
pseudocysts. rather than true cysts. They may have an attachment to the articular capsule, but rarely,if ever, communicate with the joint space. Synovial cysts,

on the other
hand, are true cysts lined
by synovial cellsand may or may
not communicate with the joint cavity(2). They arise from
herniated articular synovium, adventitial bursa, or tenosynovium. Whether trauma is an important event in the formation of some ganglia or synovial cysts
is uncertain.
Clinical Features. Although the vast majority of ganglia and synovial cysts (G-SC) occur about the wrist,they
may rarely arise in the vicinity of the temporomandibular
joint (TMJ), where they are almost invariably mistaken
for parotid tumors(3-16). The clinical featuresof 14 such
cases are summarized in Table 2. Analysis of this data
indicates that G-SC are more common in women (79%
ofall cases), affect both joints about equally and have
thus far been described only in adults from 22to 64 years
of age (average 42 years).
Although typically unilateral and juxta-articular, Farole
and Johnson reported a patientwho had bilateral, synchronous G-SC of the TMJ (14). Pate1 et al. described another

patient who had an intraosseous G-SC of the mandibular
condyle, with no evidence of predisposing degenerative
joint disease (6).
AG-SC of the TMJcharacteristicallypresentsasa
painless, slowly enlarging, soft-to-firm, preauricular mass
that doesnot interfere with movement of the jaws or cause
facial nerve dysfunction. A few individuals, however, have
complained of pain, especially on direct pressure. Others
haveexperienceda“popping”
or “clicking”sensation
when the jaws are fully extended.
Radiography. Radiologic

studies
characteristically
show a para-articular soft-tissue mass that may be either
unilocular or multilocular. Focal erosionof adjacent bone
is not uncommon.
Treatment and Prognosis. Surgicalexcision is the
treatment of choice. Because G-SC are rarely suspected
clinically, both the patient and surgeon are mentally prepared for removal of a suspected deep lobe parotidtumor.
There are, however, some clues that should suggest a GSC. In addition to its cystic appearance and para-articular
location, G-SC tend to be located at the superior border
of theparotidgland(highpreauriculararea)
and often
decrease in size when the mouth isopened,owingto
retraction of the lesion into the masseter region (9). Most
parotid neoplasms, on the other hand, are not cystic, do
not change in size on physicalmanipulation, and are
located at the angle of the mandible (15).
Follow-up and long-termprognosison G-SC of the
TMJ are virtually nonexistent. The only exception is the


Barnes

I066

al.

Table 2 Clinical Features of Ganglia and Synovial Cysts o f the Telnporomandibular Joint
Age
(yr)

sex

3

41

F

1,

2.0

4

SO

28
45
36

M
F
F
F

R
R
R(I0)
R

-

S

R
L
R
L

3.0
2.5
I .S
I .o

Ref. (sec. 1 3 . )

6
l

Side"

Clinical
S I X (cm)

2.5
I .S
3.0

H

9
IO
II

30
61
28
60

F
F
M
F

12

33
S8

F
F

R
L

I .o
I .o

13
14

22

IS

S4

M
F

B
R

2.0
4.0

I6

33

F

L

I .S

.'R. right; L. Ictt; U. bilateral: IO.

SymptoIn(s)
Relative asyn1ptomatic. occasional pain

on touching or opening the mouth
Painless mass
Painless
swelling,
slowly
enlarging
Painful mass
Intermittent cheek pain. popping sens3tion on opening jaws
Progressively enlarging, painless mass
Asymptomatic Inass
Painless tn;Lss
Painless mass. "clicking" sensation on
opening J W S
Painless IllilSS
Intermittent swelling assoc~ated with
pain on palpation or movement ofjaws
Painful mass on opening the jaws
Swelling
associated
with "popping" scnsatton when mouth was openedwidely
Slowly
enlarging,
painful tnass

intraosscous.

case of Shiba et a l . ( I O ) In this instance, thelesionwas
ruptured during surgical excision spilling the contents into
the surrounding tissues. At follow-up 2 years later, there
was n o evidence of recurrence or adverse tissue reaction

tothe extravasated fluid. The incidence of recurrence
following surgical excision of G-SC i n other sites has
ranged from 17-31% ( I ) .

11. NONNEOPLASTICDISEASES OF BONE
AND JOINTS
1I.A. Osteomyelitis of theJaws
Osteomyelitis of the jaws can develop under a variety of
conditions, themost common of which is subsequent to
an odontogenic infection. This disease can be divided into
live specfic types: (a) acute suppurative osteomyelitis.
(b) chronic suppurative osteomyelitis. (c) chronic focal
sclerosing osteomyelitis, (d) chronic diffuse sclerosing
osteomyelitis. and (e) proliferative periostitis.
1I.A.1. Ac~rtcS ~ ~ p p r r ( rOstcwrr~yditis
ti\~

Etiology and Pathogenesis. Acute osteomyelitis involves primarily the marrow and, only secondarily. does i t
affect the bone trabeculae and cortex ( I ). It can occur in

response to specific infections, such as syphilis. tuberculosis, and actinomycosis ( 2 ) .Alternatively, acute osteomyelitis Inay develop following the entry ofpyogenic organisms
subsequent to fractures or penetrating wounds (2.3). However, in Western countries, most cases in the adult are associated with an infected postextraction alveolus or a pcriapical lesion (abscess, granuloma, orcyst) that has undergone
an acute exacerbation (2,4-6). In Africa, cancrum oris ( a
rapidly spreading, destructive process caused by infection
with fusiform bacilli and Vincent's spirochetes, which results in gangrenous necrosis of the orofacial tissues), acute
necrotizing ulcerative gingivitis. and periodontal disease.
are additional important etiologic factors ( 3 ) . A local inflammatory state caused by bacterial infection leads to microthrotnbotic events (7). This results in a defective microcirculation and consequent anoxia with eventual tissue
necrosis (5.8).
I n the past. Sttrl~hylo~.oc~t~rr.s
c ~ r ~ l p l r was

. s the usual causative organism (1.4). More recent studies have demonstrated that most infections arc polymicrobial. with Sfrupt o c o ( ~ ~ 1 1 . s ~. r ~ ~ 1 0 1 ~ e ~ ~ Elrhcrc.terilrtrr.
~iII~r.s~
Klohsiellu. and
Bcrctc~roit1c.sspecies being the most commonly implicated
organisms (5,6). I n some instances. a s many as four of
these have been isolated from the same patient (S). An increased number of anaerobes also play an important ctiologic role (S.9,lO).Other frequently cultured bacteria include S. ~rlrrms,Esc~hcrichitr coli, Willorrelltr p r r ~ w l ~ r ,


1067

Diseases of the Hones and Joints

F ~ r . s o b r r ~ . t c ~ r - inucler1tur11,
lrr~~
and P r l , t o . s t r ~ ~ ~ t o c or cq ~q ~- ~ . s questrum formation occur less frequently (3.S), withthe

(S).
Withthe advent of antibiotics. most periapical infections rarely proceed to an acute osteomyelitis in healthy
persons. Onthe other hand, i t becomes a more likely
complication in medically compromised patients. Persons
who are particularly vulnerable are those with diabetes
mellitus, chronic renal failure, drug dependency. inlmunosuppression, malnutrition, anemia, vitamin deficiencies.
tobacco use, malaria, and viral fevers. particularly measles
(3,5,6,1 1-14). Alcoholism, with its attendant hepatitis and
cirrhosis. also underlies many instances o f acute osteomyelitis (6).
Dental infection is less likelytobethe
source of
ostemyelitis during childhood (IS). Instead, direct spread
froman otitis media or nlastoid infection. or hematogenous dissemination of infections from elsewhere in the
body, accounts for many cases (2.12. IS). Thefactors

that determine the development o f osteomyelitis and its
progress in both children and adults include ( a ) the virulence of the organisms and size of the inoculum: (b) the
local and systemic resistance of the host: (c) the integrity
of the vascular supply: (d) the efficiency of the body's
defense mechanisms; and (e) the osteogenic potential of
the affected bone ( I S ) . In any went, an acute inflammatory process spreads so quickly through the medullary
spaces that there is insufficient time for the body to react
to theinfiltrate (16). The vascular supply is eventually
secondarily compromised as the infection extends into
the surrounding soft tissue (17). In conditions such a s
osteoradionecrosis or the osteomyelitis, occurrin,0 In conjunction with Paget's disease. osteopetrosis, or advanced
cemento-osseous dysplasia, hypoxia induced by compromiseof the blood vessels isthe initiating, rather than
consequential, event. Because the pathogenesis ofthe
osteomyelitis associated with these latter disorders thus
differs from that related to the other causes identified i n
the foregoing, it is n o t included in this section.
ClinicalFeatures. Acute osteomyelitis can occur in
dentulous and edentulous areas (S). The mandible. generally the body. is affected more commonly than the maxilla
(S). The rarityof maxillary osteomyelitis hasbeen ascribed to its more profuse blood supply (2.3.18). Lesions
of the mandible are encountered most frequently in the
third decade oflife (3). Maxillary disease. on the other
hand. demonstrates a higher incidence i n pediatric populations and often evolves as ;I consequence of cancrum oris
and acute ulcerative gingivitis (3.19).
In either location, the disease ismanifest by severe
pain, fever. chills. regional lymphadenopathy. leukocytosis. erythema or swelling. sinus formation. and a purulent
discharge (3.S,6,I6.17,19). Pathological fractures and se-

t1ll.S

'

latter exhibiting a higher frequency in the maxilla (3).
Sequestra often exhibit spontaneous exfoliation (16). Paresthesia and anesthesia are sometimes experienced,particularly if the mandible is the site ofinfection
(6,16).
Extension of the suppuration along the inferior dental
canal into the pterygoid space often results in nlarked
trismus ( 6 ) .
Radiography. For conventional plain radiographs,
approximately 3O-S0% of bone substance mustbelost
before changes can be recognized (6). Therefore, the
radiographs may appear virtuallynormal until the osteomyelitis has been present for at least 7-10 days from the
onset of symptoms(12.20). At thattime.the trabeculae
become indistinct, and irregular radiolucent areas begin
to appear (3,14,16; Fig. 17 B ) . Sequestra, involucra, and
subperiosteal neo-osteogenesis may also be visualized
occasionally (3,I6). Computed tomography (CT) also
shows either a normal bone pattern or slightly osteolytic
changes (2 I ).
Scintigraphy is particularly sensitive after the tirst 3
days following the onset of symptoms (22) but, in some
instances. an increased activity indicative of bone involvementInay even precede clinical manifestations (23.24)
and heraldthe presence of osteomyelitis before osseous
changes are apparent onplain radiographs (25). Despite
this sensitivity, reports of false-negative results with technetium (Tc) scanning have appeared (26). Therefore,when
9y'11Tcscanis
nondiagnostic, but osteomyelitis isstill
suspected clinically, a gallium 67 citrate scancanbe
performed to confirm orexclude the presence ofthe
disease (27.28). Gallium imaging is more efficient early
i n the course of osteomyelitis, but should be reserved for

use after a negative or equivocal technetium scan (12).
Imaging with indium 111 oxine-labeled white blood cells
detects changes even before technetium scanning (29).
Magnetic resonance imaging (MRI) is another modality
that is highly useful in disclosing affected areas of bone.
as well as in evaluating a residual area of infection.
Additionally, it can provide detailed information relative
t o the extent of involvement better than that established
by conventional radiography, computed tomography, o r
bone scintigraphy (21).
Pathology. The medullary spaces are infiltratedwith
numerous neutrophils (see Fig. 17A). Eventually. the adj,cent trabeculae of bone lose their viabilityand demonstrate ragged areas of resorption. a loss of their peripheral
border of osteoblasts, and a disappearance of osteocytes
from the lacunae. Necrotic debris and bacterial colonization may also be apparent.
Treatment and Prognosis. In all instances. malnutrition. if present, should be corrected and a l l associated


1068

Barnes et al.

Figure 17 Acute suppurative osteomyelitis: (A) Numerous intact
anddegeneratingneutrophils are present in themedullary space
(H&E, X 200). (B) The trabecular patternis indistinct and sequestrumformation 1s evident(arrow). (B, courtesy of MEl-Attar,
Unlverslty of Pittsburgh School of Dental Medicine, Pittsburgh,
PA.)

to infection. Furthermore, the response to the osteomyelitis
debilitatingdiseases must betreated (3). Conservative
in this instance may be attenuated so that the diagnosis is

management of the osteomyelitisitself consists of drainage
delayed until the infectionis advanced (6).
and the administration of appropriate antibiotics, as deterThe development of sequestra is frequentlyencounmined by microbial
culture
and
sensitivity
tests
tered. When small, thesemay be exfoliated spontaneously.
(3,5,16,30). The exact duration of antibiotic treatment reSome authors recommend sequestrectomy for larger ones
quired is difficult to establish, and the recommended time
(3,5,12), whereas others have concluded that this procehas ranged from 2 weeks to6 months (5,12,31). A variety
dure is not necessary in all cases because, under favorable
of antibiotics havebeen employed, the advantages and discircumstances, even fairly large sequestra can be rendered
advantages of which have been discussed by Ord and El
sterile by antibiotic therapy (4).Other types of surgical
Attar (1 2). Calhoun et al. (5) found no significant differprocedures that have been used include complete removal
ences in cure rate based on the choiceof antibiotics, numof diseased bone, tooth extraction, and fracture fixation
ber of antibiotics, or duration of antibiotic administration.
( 3 3 , as well as decortication and resection (3,6). Tooth
Davies and Cam recommend that patientswith a history of
extractionislimited
to thoseteeththathavelosttheir
alcohol abuse be premedicatedwith antibiotics beforeany
bony support, and it is carried out in conjunction with
dental extractions because these individuals are more prone


1069

Diseases of the Bones and Joints

curettage and sequestrectomy (3). Resection is performed
only when the buccal and lingual cortical plates are
destroyed and there is no evidence of new bone formation
(3). it is followed by the placement ofaniliac
bone
(4). The combination of antibiotics with
or ribgraft
metronidazole. which is particularly effective against aerobic organisms, hasbeen quite useful (3). A system consisting of theuseofsurgical
intervention and antibiotic
treatment basedonthe
stage ofthe disease (degree o f
bone involvement) after correction of any underlying
systemic disorder hasbeen developed by Calhoun et a l .
(5).
Hyperbaric oxygen has been used a s an adjunct in the
treatment o f acute osteomyelitis (32). With this modality.
anaerobic pathogens are destroyed and sequestration of
necrotic bone occurs without suppuration and with less
bone loss (12). I t has also beenusefulwhenused
in
patientswith underlying medical problems and in those
i n whom other forms of treatment have failed (S). However, its disadvantages lie i n its high cost, the shortage of
facilities. frequency o f required treatment. and possible
side effects on the central nervous system (12).
Periostitis. soft-tissue abscesses. or cellulitis. a s well
;IS pathological fractures represent potential sequellac of
untreated or uncontrolled acute osteomyelitis.
DifferentialDiagnosis.
Distinction should bemade

between the osteomyelitis described in this section and
the one termed acute maxillitis of infancy by Hitchin and
Naylor (33). This latter condition was first described by
Rees i n 1847 (34). and it has also been referred to ;IS
acute neonatal maxillitis (35). It is an uncommon disease
characterized by the development of ;I diffuse, destructive.
O S S ~ O L I Sinfection of the midface during the first weeks of
life. Comprehensive descriptions and reviews of the various features of this disorder havebeenpresented
by
several authors (33.35-5 I ) . The child develops restlessness and fever, followed by cdetna and erythema ofthe
periorbital region and eyelids. Chemosis and cot1.junctivitis
are common, and exophthalmosor proptosis may also
occur in some cases. Ultimately.an abscess develops i n
the orbit and drains through fistulae at the inner canthus.
As the disease progresses, a mucopurulent nasal discharge.
whichis increased by pressure onthe bulbus oculi, becomesevident.The palatal mucosa onthe affected side
becomes brightred
and is pathognomonically sharply
demarcated fromthenormal
side by themedian raphe.
Abscess formation, sinus tract development. a suppurative
discharge. sequestration of tooth germs. and the establishment of an oral-nasal fistula follow soon thereafter. Nccrosis of tooth germs takes place and is reflected by hypoplastic enamel and attrition o f the permanent dentition i n later
life. Premature eruption of teeth has also been noted.

Although it is generally agreed that the inciting organism in acute maxillitis of infancy is S. aurous. doubt still
exists relative to the portal of entry and the route followed
by this microorganism. Hematogenous dissemination from
near or distant parts. as well as origin from a mastitis in
the mother or from infected wounds onthe hands of
attending nurses, have been proposed. A break in the oral

mucous membranes would permitbacterial invasion of
the jaw, with subsequent spread tothe orbit through the
tooth germs. Alternative possibilities include extension
from the nose or lacrimal duct intothe maxillary sinus
and then spread to both the orbit and tooth germs.
Therapy consists of the establishment of drainage i n
conjunction with intensive antibiotic therapy and supportive treatment. A mortality rate of from 4 to 15% has been
reported. despite the availability of antibiotics (36,42). In
those who survive the disease, permanent cyc damage is
a distinct possibility (37).
ll.A.2. Chrorlic Supprutille 0 . s t c w r y d i t i . s

EtiologyandPathogenesis.
This form of ostcomyelitis may developde novo or following the subsidence
ofthe acute phase of the disease. For inclusion i n the
latter category, thelesionmustbeofatleast
I-month
duration to reflect either a lack of response to the initial
therapy or an overpowering o f the host defenses (13,43).
Most infections are polymicrobial. and no specific microorganisms have been found to be a predominant etiologic
agent (19).
I n chronic suppurative osteomyelitis. thc host's response to infection results in the production ofhighly
vnsculnr granulation tissue thatis eventually converted
into scar tissue. During this transformation the granulation
tissue becomes avascular and forms an impermeable wall
around the infected area (dead space), with the normal
bone spaces acting as bacterial reservoirs. This results in
a persistent focus ofinfectionthatisprone
to repeated
episodes o f acute exacerbation (4.16). I n addition. the

infection-induced thrombi of small vessels (7) leads to a
defective microcirculation which, i n turn, causes anoxia
and its consequential tissue necrosis (5.8.44)
ClinicalFeatures.
The highest frequency is i n the
body and angle ofthe
mandible (19). Males may be
affected three times as often as females ( I C ) ) , or there may
be an equal gender distribution ( 14,45). I n one studyof
23 cases, 65% occurred in thesixth through the eighth
decades ( 14). The age varies from I3 to 88 years ( 14.19).
withthemean
falling in thefifth (19.45) or sixth (14)
decade.
Swelling. pain. and draining fistulae constitute the most
common manifestations. Symptoms of acute disease. such


1070

as fever and leukocytosis, are typically absent (19). Destruction of bone and the formation of sequestra may
continue
(4,16,19),
and infection-induced thrombotic
involvement of a single feeder vessel can lead to necrosis
of a large segment of the affected bone ( 1 6). Pathological
fractures, malocclusion, trismus, or loose teeth are less
frequently encountered (16,19). Anesthesia or paresthesia
is quite rare (46).
Radiography. This form of osteomyelitis produces

an ill-defined radiolucency that often reveals focal radiopaque areas, thus imparting a “moth-eaten” appearance
(16,46). Sequestra are likely to be present (16,21) Occasionally. the surrounding bone exhibits an increased density, and the cortical surface may exhibit a periosteal
reaction ( 1 6). Magnetic resonance imaging (MRI) is valuable in evaluating residual areas of infection and in providing detailed information concerning the extent of involvement better than conventional radiography, CT scan, or
scintigraphy (21).
Pathology. The histological appearance of chronic
osteomyelitis is dependent on the severity of the disease.
I n mild cases, only a few lymphocytes are embedded i n
thefibroticmarrow.
Irregular bony trabeculae maybe
present, together with occasional osteoclasts and osteoblasts. In more severe cases, sequestra and reversal lines
are more likely to be apparent. Osteoclastic activity is
more prominent, inflammatory cells are more abundant,
and focal abscesses are common (16,46).
Treatment and Prognosis. The fundamental management of all cases of chronic osteomyelitis entails the
implementation of various types of surgical procedures,
as dictated by the extent of the disease, in conjunction
withtheuse of appropriate antibiotics (4,5,16,19,30,4749). In small lesions curettage, sequestration, and saucerization constitute theusual
mode of treatment. When
larger segments of bone are involved, decortication or
saucerization are often used, together with the transplantation of cancellous bone chips. The presence of persistent
chronic osteomyelitis, extensive bone loss, or pathological
fractures necessitates a resection of the involved area,
followed by immediate reconstruction with an autologous
bone graft (16,30). The dissemination of systemically
administered antibiotics is often impeded by two factors:
(a) thrombi withinthe microcirculation, and (b) obstruction of access to the infected area by the dense fibrous
wall surrounding the dead space (4,7). The high doses of
antibiotics that have been required to compensate for these
impediments often produce undesirable side effects (SO).
However, treatment with antibiotics or streptokinase concomitantly withheparin can overcome the problems of

drug delivery introduced by activation of the blood coagulation and fibrinolysis system (44). Furthermore, the direct

Barnes et al.

insertionof polymethylmethacrylate beads impregnated
with gentamicin (S 1-53) or tobramycin (50,S4) produces
high concentrations of antibiotics in a localized site without the possible deleterious effects that high levels might
have on various organ systems (SO). Because different
antibiotics appear to reach a level of maximum release at
different intervals ( 5 1,55-57), the time the beads should
be permitted to remain in situ depends on the antibiotic
used (SO). The indications for the use of these beads are
(a) an infection that has been refractory to previously
attempted traditional treatment; (b) a decreased blood flow
to the infected area; (c) an inmunocompromised host; (d)
the presence of medical conditions (hepatic andrenal
dysfunctions) that would not allow the use of high doses
of oral or intravenous antibiotics; and (e) patients who
cannot be relied on to take the prescribed antibiotics (50).
The results of hyperbaric oxygen alone or in conjunction with antibiotics or antibiotics and surgery vary from
demonstrating a marked improvement to a complete cure
( 1 2,30,58-60).
An MRI scan is useful in guiding surgical debridement
because of its ability to differentiate between active inflammation and chronic fibrosis and to detect noncontiguous areas of involvement (2 1.61 ). Scintigraphy ( 1 6 3 9 )
and repeated measurements of serum levels of CUI -antitrypsin, orosomucoid, and haptoglobin (62) can also be
usedto follow the progress of treatment. The synthesis
of these particular proteins in the liver is regulated by
inflammatory mediators, such as interleukin- 1, interleukin-6, tumor necrosis factor. prostaglandin E,, and leukotriens in the affected areas (62).
II.A.3. Chronic Focd Sclrrosirlg 0stconlgeliti.s

Etiology and Pathogenesis. Chronic focal sclerosing
osteomyelitis (CFSO), also referred to as condensing osteitis, represents a hyperplastic reactionof bone to a mild
bacterial infection ( I ) . The ensuing sclerotic bone arises as
a consequence of excessive apposition o f the bone trabeculae without concomitant resorption (2). The portal of entry
is through an inflamed or necrotic pulp that has developed
in a tooth secondary to a deep carious lesion, a large restoration ( 1,3) or, less frequently, a cracked tooth (4).
Clinical Features. CFSO has been seen in about 78% of dental radiographs (5,6) and constitutes 7% of all
periapical lesions (3,7.8). Some authors have reported a
female preponderance (3,5), whereas othershave found
no significant gender difference (1,9). It is most commonly
found in the mandible (3,8,9), the first molar being the
predominant site (9,lO). Other thanmildpainrelatedto
the infected pulp, there are generally no signs or symptoms
associated with this condition (1,4). As a reflection of the


1071

Diseases of the Bones and Joints

Figure 18 Chronic focalsclerosingosteomyelitis: (A) A welldefined radiopaque mass (arrow) is present adjacent to the apices
of the mandibular firstmolar. (B) Histologically, the lesion consists
of a densemass
of bonytrabeculaeandinterveningfibrous
connective tissue. Inflammatory cells are sparse in this particular
section (H&E, X 100). (A, courtesy of WG Fischer, University of
Pittsburgh School of Dental Medicine, Pittsburgh. PA.)

pulpalnecrosis, the affectedtoothdoes not respondto
vitality tests.

Radiography. CFSO presents as a radiopaque periapical mass of sclerotic bone. The borders of the lesion
may be smooth and well-defined, or appear to blend into
thesurroundingbone(Fig.
18A). Theadjacenttooth
exhibitsacontinuous,oftenthickenedperiodontalligamentand,sometimes,aconcurrentapicalinflammatory
lesion ( 2 4 1 1 ) . External root resorption is present
in a
small percentage of cases (3,lO).
Pathology. Microscopic examination reveals a dense
mass of bony trabeculae, which may or maynot
be
bordered by osteoblasts, dependingon the degreeof activity present at the time of evaluation. The intervening soft
tissue, if present, is usuallyfibrotic and is occasionally
infiltrated by scattered lymphocytes (1; see Fig. 18B).
Treatmentand Prognosis. Managemententails either extractionor endodontic therapyof the involved tooth.
In endodontically treated teeth, regressionof the lesion accompanied by normalization of the periodontal ligament
has been noted in 85% of cases (3). In some instances, remodeling does not take place, even following extraction

and thus may persist radiographically foran indefinite period (7,12; Fig. 19). This residual area of sclerosis is referred to as a bone scar
(1 1). Its surgical removal isnot required unless it becomes symptomatic
(1).
Differential Diagnosis. Radiographically, CFSO
must be distinguished from a cementoblastoma, hypercementosis,periapical cementa1 dysplasia,focalcementoosseousdysplasia, and an ossifyingfibroma (10). The
criteria used foraccomplishingthesedistinctionshave
been discussed in other sectionsof this text. Focal periapical osteopetrosis must also be considered in a differential
diagnosis. This is a radiopaque lesion that develops in the
periapical region of teeth in which no pulpal insult can
be demonstrated; that is, in association with noncarious
teeth or with teeth having only small carious lesions
or

restorations (10). A review of sequential radiographs can
be used to rule out the possibility of a retained root (1 3).

II.A.4.

Chronic Diffuse SclerosingOsteomyelitis

Chronicdiffusesclerosingosteomyelitis(CDSO)isa
poorly understood disease that differs from the usual form


1072

Barnes et al.

l

Figure 19 A residual area of chronic focal sclerosing osteomyelitis. (Courtesy of WG Fischer, University of Pittsburgh School
of Dental Medicme, Pittsburgh, PA.)

of chronic osteomyelitis by the absence of pus or fistula
formation and therefore, is sometimes referred to as nonsuppurative osteomyelitis (1) or osteomyelitis sicca (2).
Etiology and Pathogenesis. The fundamentalnature
of CDSO is unclear, and the literature is replete with
conflicting philosophies and terminology. Although infection, probablyof dental origin (periodontitis; pericoronitis,
periapical inflammatory disease) has
been the predominant
consideration ( l ,3-5), there has been considerable difficulty in substantiating this concept owing to the inability
to consistently isolate a noncontaminant, causative microorganismfromthelesion.However,asaresult
of the

success of their more stringent techniques, Marx et
al. (6)
havepresentedevidencetosupportthecontentionthat
CDSO represents a specific infection producedby Actinomyces or Arachnia species, together with gram-negative
anaerobic pathogens, of which Eikenella corrodens is the
most common. The resultantdisease is nonsuppurative
and produces an endosteal and periosteal sclerosis of the

mandible in conjunction with pain. Thesclerosisis
thought to be precipitatedby a reaction of medullary bone
tothepresence
of thesemicroorganisms,whereasthe
discomfort may be related to the medullary inflammation
or bone ischemia (6,7). Other proposed possibilities includereactivehyperplasia
of bone (8), painfulfibroosseousdiseaserelated to fibrousdysplasia (9,10), and
hyperactive immunological response(1 1,12). An extensive
presentation of the pros and cons of each of these factors
has been presented by Marx et al. (6). More recently, van
Merkestyn et al. have suggested that CDSO,
or at least
some cases thereof, actually represents a chronic tendoperiostitis that develops in responseto overuse of the masseter or digastric muscles secondary to parafunctional habits,
such as bruxism, nail-biting, or clenching (13). Neville et
al., on the other hand, consider
CDSO and tendoperiostitis
to be separate disorders and suggest that many reported
cases of the former condition actually represent the latter
(5). These same authors also describe CDSO an
asasymp-

Diseases of the Bones and Joints

tomutic condition. a concept that represents a marked
departure from the established viewpoint that has been
traditionally presented.
Until these and other diverse issues are more completely
resolved. i n the discussion that follows. we will adhere t o
the more conventional information and precepls contained
i n the series o f articles published by Jacobsson and his colleagues (3.4,7,15-17), as well ;IS by Schneider and Mesa
( 1 8). Tsuchimichi. et a l . ( IO), and Marx et a l . (6).
Clinical Features. CDSO is characterized by a localized swelling and repeated eplsodes of pain, both of which
arc unilateral and restricted tothe mandible. Swelling
along the lower border of the mandible owing tohigh
periostealreactivity is ;I prominent feature in the carly
stages, particularly among younger patients. Exnccrbations occur at intervals thatvaryfrom
months to years
and generally last for 1-3- weeks. Theepisodes o f pain
are more frequent and more severe in earlier periods of
the disease. Fistula formation or sequestration arc not
encountered. Trismus may develop i n patients i n whom
the pathological process encroaches onthe temporomandibular joint. Extension
from
the
initial
mandibular
involvement i n t o the zygomatic arch and temporal bone
may also occur i n rare instances. The erythrocyte sedimentation rate has been elevated during periods of exacerbntion, but other laboratory tindings are within normal limits.
The disease can appear at any age. but is most common
i n young adults, themean age being 27 years. Females
are affected three to four times a s often a s males.but

there is no racial propensity.
Radiography. The lesion appears ;IS mixed osteolytic
and sclerotic zones. In the later stages o f the disease,
sclerosis is the predominant feature. Periosteal deposition
of bone is frequently apparent, especially during acute
episodes i n younger patients. The lesionisnot restricted
t o the tooth-bearing parts of the mandible. but can extend
fromthe alveolar ridge t o the inferior border and can
affect the ascending ramus, including the condylar process. Shortening of the roots o f teeth i n the affected areas
is frequently observed.
An increased uptake of"""'technetium polyphosphnte
or diphosphonate has been demonstrated i n the diseased
sites. Zones with especially intense isotopic activity corrcspond well with osteolytic areas. Scintogrnphy is a valuable diagnostic tool because it provides a more distinct
demarcation of the lesion than a standard radiograph and
1'.'ICI.'I' ltates the detection o f an extraosseous extension.
Pathology. Four types of tissues have been identitied
histologically. depending on the depth at which the biopsy
is obtained (7.15): ( a ) severely sclerotic bone. with narrowed haversian canals. and ;I mosaic pattern indicative
of previous remodeling these features arc seen in the

1073

peripheral parts of the lesion. (h) Coarse. irregular bony
trabeculae, with fibrotic marrow spaces containing scattered lylnphocytes and plasma cells; multinucleated ostcoclasts are present along the borders of thc trabeculae:
markedly widenedblood
vessels are see11 adjacent t o
amorphous, necrotic. or osteoid areas; this entire second
pattern constitutes the most characteristic changes associated with CDSO. ( c ) Proliferating bony trabeculae that
resemble those seen i n fibrous dysplasia are embedded
i n a highly vascular, cellular fibrous connective tissue.

intiltrated with occasional lymphocytes and plasma cells.
(d) Granulation tissue, without any hard tissue. but cxhibiting abundant perivascular lymphocytes and plasma cells
as well as osteocI;1sts: thispatternis
sometimes seen in
the deepest parts of the lesion.
Although these features may be characteristic. they are
nonspecitic and often subtle. Consequently. it mustbe
emphasized that a definitive diagnosis requires the integration of pathological findings into information derived from
clinical and radiographic assessn1ents.
TreatmentandPrognosis.
CDSO characteristically
follows a markedly protracted course i n spite o f therapy
that occasionally persists throughout the lifetime of the
patient (7,20). It canbe a serious debilitating disease
that, i n some instances, hasledto
narcotic addiction or
emotional disturbances (6). Spontaneous remissions are
infrequent. Factors thathavebeen
proposed to affect
the inception and progression of the disease include the
virulence of the causative microorganism, the anatomical
possibilities of the spread of infection. and immunological
and tissue responses (4,12).
The administration of corticosteroids (3) or disodium
clodronate, an inhibitor of bone resorption ( 2 I ), has been
reported to be helpful in relieving the symptoms i n some
cases o f CDSO. Several additional therapeutic approaches
have been employed in the management of the lesions occurring during the periods of acute exacerbations. olicn
with only minimal success in alleviating discomfort or prcventing their subsequent reappearance. These include the
use of antibiotics, hyperbaric oxygenation. radiation thcrapy, analgesics and sedatives. and removal of infectious

foci and sequestra (3,23--25). Severe cases havebcen
treated by decortication o r resection o f the affected areas
(9,26-29). The success rate lollowing decortication is approximately 50% (O,29). I n most instances of failure,
symptoms recur within I year postoperatively. Sex, location, extent of symptoms, and duration of the disease do not
appear t o affect the result of treatment. On the other hand.
age and the presence or absence of teeth i n the decorticated
area correlate with the outcome. Patients who exhibit improvement are significantly older a t the onset of symptoms
and. at the time of surgery, are considerably more likely to