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

(BQ) Part 2 book Surgical pathology of the head and neck - Vol 2 has contents: Diseases of the bones and joints, hematopoietic and lymphoid disorders, the pathology of neck dissections, the occult primary and metastatic tumors to and from the head and neck.

Robert S Verbin* and Billy N Appel*

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

1 Diseases of the Joints 1 x o r 1 B a r w s

A Rheumatoid Arthrltis

B Gout

C Calcium Pyrophosphate Dihydrate

D Synovlal Chondromatosis

E Piglnented Villonodular Synovitis

F Ganglia-Synovial Cysts of the Temporomandibular Joint

Crystal Deposition Disease (Chondrocalcinosis, Pseudogout)

11 Nonneoplastic Diseases of Bone and Joints Ro1wr-t S W h i t l , Lro,l Brrrrws

t r r d Hi/!\ N AppcI

A Osteomyelitls of the Jaws Rolx)r/ S K,r-hirr

B Osteoradionecrosis LCWI Bt~r-ne.s

C Relapsing Polychondritis Lcorr Borne.s

D Focal Osteoporotlc Bone Marrow Defect Ro1wr-r S V e r l h

E Cortlcal Defccts 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

Ill Neoplastic and Neoplastic-like Diseases of Bone Leon Btrnzes ntld Rohc~r-t .S Wrhirz

A Solitary Hcmnngioma o f Bone L e o r r B a r w s

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

G Osteoid Osteoma Leorr Uorrre.s

H Osteoblastoma L c w ~ H t r n l e s

I Ossifymg Fibroma Rober-? S Uvhiu

J Chondroid (Cartilaginous) Metaplasia of the Larynx Leotl Hrrme.s

K Chondroma and Chondrosarcoma of the Larynx I x o t l Ranzc s

L Chondroma and Chondrosarcoma of the Jaws and Craniofacial Bones Leorr Hrrr7w.s

M Chondrosarcoma of the Skull Base Leon Rtrr-~re.~

N Chondromyxotd Fibroma L c ~ r r Rrrr-ties

0 Chondroblastoma Leorr Brrr-rws

P Chordoma Lwrl Wrrrrw.s

Q Giant Cell Tumor Leon Rcrr-~(,s

R Giant Cell Granuloma Roher-I S Uvhirr

S Aneurysmal Bone Cyst Leorl Btrrnc.,s

T Desmoplastic Fibroma Leon Rarnc~.s

U Fibrosarcornn L w r ~ Bnrrres

V Osteosarcoma o f the Jaws, Skull and Larynx L c w Narrrc s

W Juxtacortical (Surface) Osteosarcoma Leon B~rr-rres

X Extraosseous Osteosarcoma Leon Uanrc~,s

Y A n g m x c o m a of Bone LNNI B ~ I ~ I I P S

Z Ewing’s Sarcoma Lcofr /hrr-~rc.s

References

I DISEASES OF THE JOINTS

I.A Rheumatoid Arthritis

Introduction Rheumatoid arthritis (RA) is a chronic

systemic disease characterized primarily by nonsuppura-

tive symmetrical inflammation o f peripheral synovial

joints Extra-articular manifestations however are fre-

quent 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)

Clinical Features There are many common and un-

common manifestations of RA in the head and neck (4)

Among these are the following:

I k ~ r w r

Involvement of the larynx by RA is not unexpected be-

cause 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 the most 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

112s

I l27

I130

1136 11.77

1142

I145

I l46 I14X

117.3

1178

1 1 x 1 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 on indirect and 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 laryn- geal signs and symptoms In one series of 64 randomly selected patients with RA of 9 years average duration

(range 9 months to 35 years) 17 (27%) had laryngeal

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, full- ness or tension in the throat, dyspnea referred otalgia ody- nophagia, stridor, dysphagia, and painful speech (7) De- pending 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

Diseases of the Bones and Joints 1051

Cartilages of the Larynx

Hyoid bone Epiglottic cartilage

Arytenoid cartilage

Cricoarytenoid joint Thyroid cartilage

Cricoid cartilage Cricothyroid joint

between the extent of involvement of the cricoarytenoid

joint and symptomatology is not reliable, for some patients

have shown severe joint disease and had no symptoms,

whereas others have had no physical findings, but promi-

nent symptoms (6,9) In general, patients who are symp-

tomatic are more likely to have physical findings

One of the most-feared complications of laryngeal RA

is ankylosis of the cricoarytenoid joints in a state of

Figure 1 Diagram showing normal cartilages and joints of the larynx

adduction This results in significant narrowing of the glottis, and any superimposed upper respiratory infection,

no matter how trivial, may result in acute airway obstruc- tion and the need for emergency tracheotomy

2 Temporomandibular Joint

Of the patients with RA, 50-75% will have involvement

of the temporomandibular joint ( T M J ) (18-21) When

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

present, the joint involvement is usually 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 move-

ment 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 mal-

occlusion 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 (dry eye)

component of Sjogren’s syndrome, RA may manifest in

the eye a s iritis iridocyclitis, and scleritis In most in-

stances these are late manifestations of the disease

4 Ecw

Hearing impairment in patients with RA is a subject of

controversy, and its nature and extent has not been fully

delineated (22-28) Since the incudomalleal and incudo-

stapedial articulations are synovial joints with cartilagi-

nous articular disks one would assume that they would

be subjected to the same ravages of RA a s seen in small

joints elsewhere i n the body (37) Surprisingly, there have

been very few histological studies of the 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 2 6 4 8 % of

patients and is 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 sensori-

neural deafness (23)

Although patients with RA frequently manifest an in-

creased “stiffness” of the ossicles on specialized testing,

clinically significant conductive hearing loss is unusual

(28) Some drugs used in the treatment of RA, especially

salicylates, are potentially ototoxic and may also contrib-

ute to hearing abnormalities

S Nose

In rare instances, patients with RA may experience sponta-

neous perforation of the nasal septum (31,32) Although

presumably caused by vasculitis or local vasospasm, biop-

sies from the edges of these ulcers have not shown evidence of vascular damage

6 S u l i ~ ~ r r y Glands: Sjogrer? ‘ S S y c l r o t w

Fifteen to 2.5% of patients with RA may manifest Sjo- gren’s syndrome, an idiopathic immunologically medi- ated, inflammatory-destructive disorder of the lacrimal and salivary glands, leading to dry eyes and mouth This syndrome is discussed i n greater detail i n Chapter 13

Pathologists should be aware that patients with RA who are treated with a combination of methotrexate and predni- sone may develop an Epstein-Barr virus lymphoid prolif- eration 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 titers of 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

i t occurs the true vocal cords appear to be the most frequent site ( 3 8 4 1 ; Fig 3) They have also been de- scribed 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 to yellow-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, i t may be impossible to separate from polyarteritis nodosa

on histological examination alone Vasculitis is usually associated with rheumatoid nodules and high titers of rheumatoid factor I t is thought t o be the result o f immune

complexes and usually manifests as cutaneous-mucosal ulcers or a neuropathy (3,10,42.43)

Diseases of the Bones and Joints 1053

10 Neuropathy

The complication of neuropathy, which may be sensory or

motor, occurs in about 10% of patients with RA In some

instances, this is related to a small vessel angiitis involving

the nutrient blood vessels (vaso nervorum) of nerves, re-

sulting in demyelination or even frank necrosis A com-

pressive (entrapment) neuropathy accounts for most of the

remaining cases, such as in the carpel tunnel syndrome

Involvement of the cervical spine is recognized to be a

common manifestation of RA and typically appears late in

the course of the disease (44,45) Although about 25% of

patients will exhibit radiographic abnormalities of the cer-

vical vertebrae (usually varying degrees of subluxation),

only a few will ever develop neurological symptoms (44)

11 Myopathy and Myositis

Muscle atrophy in RA may be due to disuse or ischemic

neuritis-vasculitis (as noted earlier) The latter often re-

sults in focal or diffuse demyelination with subsequent

neurogenic atrophy

One may also see nodular collections of chronic in-

flammatory cells, principally lymphocytes, lying within

the muscle, which may also contribute to muscle weak-

ness In contrast with dermatomyositis, these inflamma-

tory foci are not associated with regenerative muscle

changes or necrosis

Figure 3 This 66-year-old coal miner, with a 12-year hlstory of rheumatold ar- thritis, died of respiratory failure second- ary to anthracosilicosis and pulmonary fibrosis An autopsy revealed bilateral rheumatoid involvement of the cricoary- tenoid joints and rheumatoid nodules In the soft tissue of the glottis and sub- glottis The glottic nodules are illustrated Thyroid cartilage containing marrow is present in the lower left hand comer (he- matoxylin and eosin [H&E] X50)

(Courtesy of G Perkins, University of Westem Ontario, London, Ontano and R

Kessler, Montefiore Hospital, Pittsburgh, PA.)

12 Amyloid

Amyloid may develop in up to 20% of patients with RA This subject is discussed in greater detail in Chapter 30 Pathology The pathology is identical with that ob-

served in peripheral joints Early in the course of the dis- ease, the synovium is congested, edematous, hyperplastic, and extensively infiltrated with plasma cells and lympho- cytes As the abnormal synovium (pannus) enlarges, it ex- tends over the articular surface and destroys the cartilage, predisposing the joint to the ravages of secondary degener- ative joint disease As the disease progresses, the pannus may become fibrotic or even ossify, resulting in a “frozen”

Treatment In general, medical treatment of the sys-

temic disease will alleviate or ameliorate many of the head and neck manifestations Some of the problems, however, may have to be approached surgically Some patients with severe cricoarytenoid arthritis may experi- ence ankylosis of the joint(s) with fixation of the vocal cords in a state of adduction and significant airway com- promise In these instances, arytenoidectomy with vocal

Figure 4 Rheumatoid nodule composed

of a central zone of fibrinoid necrosis

and a penpheral border of histiocytes,

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

urate crystals As the disease progresses, the joints become I.B Gout progressively deformed, and urate deposits become ~~

Introduction Gout, which may be primary or sec-

ondary, is a disorder of purine metabolism characterized

grossly visible as tophi (Figure 5) The disease is not uncommon, for about 5% of patients in major arthritis

clinics are estimated to have gout (1)

Figure 5 Gouty tophus on the helix

of the ear (arrow) (Courtesy RE Lee,

Unwersity of Pittsburgh Medical Cen-

ter, Pittsburgh, PA.)

d

Diseases of the Hones and Joints 1055

In humans, who lack the 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 i t 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 used to describe those individuals whosc hyperuri-

cemia is due to an “inborn genetically determined meta-

bolic defect leading to a pathologic de novo biosynthesis

and/or retention of uric acid” (2) Of this group about

90% are men: when i t occurs in women, most are post-

menopausal 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 with the duration and degree of elevation of the

serum uric acid level For example, i f an individual main-

tains 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 initial attack is typically monoarticular and involves

a peripheral joint usually the great toe (podagra) i n SO-

7 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, and will resolve spontaneously i n a few

days to weeks if left untreated Such attacks may be

precipitated by prolonged fasting, excessive alcohol con-

sumption surgery joint trauma or ingestion of drugs that

intcrfcre with renal excretion of uric acid (especially

thiazides)

3 lr1tvrcriticwl (lrl/c~r\wl) Golrl

Intercritical gout is the asymptomatic period between

acute attacks I t may vary from weeks to years but

most individuals will suffer another acute attack within 6

months t o 2 years after the initial attack As the disease

progresses, the attacks become more frequent and scverc,

and multiple joints may become involved

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 13-

35% ( l ) Their development is related to the length of the disease, degree of elevation of the serum uric acid, and the severity of renal involvement ( I )

In general, patients have had gouty arthritis for an aver- age of 1 0 years before tophi begin t o appear ( 2 ) Thcy arc

rarely observed at the time of the first attack The most fre- quent 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 oidiabe- tes mellitus, obesity, atherosclerosis, hypertension, and car- diovascular disease In 2 04 0% 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 other ac- quircd disease in which there is accelerated nucleic acid turnover or impaired excretion of uric acid Hcmatolog- ical malignancies hypertensive cardiovascular disease and chronic renal disease are some of the more common causes I n the secondary form there is no hereditary ten- dency scrum uric acid levels are higher, the age of onset may be younger, and there is a higher incidence in women The pathogenesis of the acute attack of gout is com- plex As the urate crystals begin to nccumulate within the joints, they are immediately phagocytosed by neutrophils which, i n turn liberate lysosomal enzymes that have ;I

destructive effect on articular cartilage In addition the urate crystals activate Hagemm factor which stimulates cytokine production, resulting i n increased vascular per- meability and a greater concentration of neutrophils The ensuing anaerobic metabolism lowers the pH which fur- ther promotes uric acid production Thus a vicious cycle

is cstablished

5 Hetrd t r t d N d Mtrr1i~sttrtiorl.s

Although gout may affect the head and neck i n any stage of

the disease, it generally occurs only in patients with long-

standing disease Tophi and cricoarytenoid arthritis are the

prime manifestations (4-10) In this region, tophi are most

often observed on the helix of the ear or in the vicinity of

the true and false vocal cords; however, they have been de-

scribed in the soft palate, uvula, glossoepiglottic fold,

tongue, hyoid bone, thyroid cartilage, epiglottis, subglottis,

tracheal cartilage, first part of the esophagus, sclera, con-

junctiva, and hypopharynx (5,6,8,10; see Fig 5 )

Involvement of the cricoarytenoid joint results in

hoarseness, dysphagia, dysphonia, pain, and possible joint

fixation, with aspiration pneumonia As might be expected,

hoarseness is the chief symptom when tophi involve the

true vocal cords Aural tophi can be confused clinically

with chondrodermatitis nodularis The presence of pain,

however, favors the latter Gouty involvement of the

temporomandibular joint is very rare

Pathology Tophi are composed of aggregates of

elongated needle-shaped, clear to light brown crystals,

often appearing as “bundles of wheat.” The crystals, in

turn, are immediately surrounded by foreign body giant

cells, histiocytes, and dense fibrous connective tissue

(3,ll-13; Fig 6 ) The crystals show negative birefrin-

gence When a primary color compensator is positioned

between two polarizing lenses, the crystals will change

from yellow to blue on rotation of the polarizing lenses

from parallel to perpendicular

When gout involves a joint, it may produce a gross

deformity, with prominent intra-articular deposits of urate

crystals and changes of secondary degenerative joint dis- eases

Differential Diagnosis The differential diagnosis in-

cludes Teflon granuloma and pseudogout Patients who have unilateral vocal cord paralysis are often treated by injecting the paralyzed cord with Teflon, which expands the cord and, thereby, improves speech and lessens the difficulty with secretions Teflon particles vary from round

to ovoid and tend to have a clear center and a thick border They also elicit a foreign body giant cell reaction and fibrosis and will polarize, which may result in confu-

sion with gout (see Chapter 5 ; Figs 18 and 19) Sodium

urate crystals, however, are thin and elongated, not round

or ovoid In addition, the clinical history, normal serum uric acid level, and negative DeGalantha stain for uric acid readily allow one to distinguish a Teflon granuloma from gout

Pseudogout or chondrocalcinosis may also be confused with gout In this disease, calcium pyrophosphate dihy- drate crystals are deposited in soft tissues or joints (14)

The pyrophosphate crystals appear as short, blunt rods, rhomboids, or cuboids that are weakly birefringent under polarized light (Fig 7)

Treatment and Prognosis Treatment consists of drugs, such as colchicine, allopurinol, probenecid, cortico- steroids, and nonsteroidal, anti-inflammatory agents de-

signed to intermpt the afore noted cycle of events or to lower the serum urate level (15) If the gout is secondary,

Figure 6 Gouty tophus composed of needle-shaped urate crystals that

have evoked a forelgn body giant cell reactlon (H&E, X 350)

Diseases of the Bones and Joints 1057

then control of the primary disease is mandatory Tophi

may dissolve with medication, but larger ones that are

disfiguring or that interfere with joint function may have

to be surgically excised Joints severely deformed by

secondary degenerative joint disease frequently require

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 antihyperuricemic therapy,

the natural history of the disease has been altered Nowa-

days, 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 S t a g and McCarty et al

were among the first to recognize and characterize the

condition now known as calcium pyrophosphate dihydrate

(CPPD) crystal deposition disease (chondrocalcinosis,

pseudogout, CPPD arthropathy: 1-4) In this disorder, for

reasons unknown, crystals of CPPD accumulate in the

joints, especially the knee, wrist, metacarpophalangeal,

hip and spine, and occasionally, the para-articular tissues

of older persons

The disease is not uncommon It has been observed

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

Figure 7 Crystals of calcium pyro- phosphate dihydrate (pseudogout) ap- pear in tissue as rhomboids, cubes, or

rectangles Note the multinucleated gi- ant cells (H&E, X400) Compare with Fig 6

ratio of 1.51 and occurs in patients averaging 72 years

ochronosis (5,6)

CPPD disease ranges from totally innocuous to inca- pacitating, 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

disease presents 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 (pseudorheuma-

toid arthritis) is characterized by multiple joint involve- ment, with subacute attacks lasting from weeks to several months This variant may be mistaken 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 large joints bilaterally and, accordingly, are frequently misdiagnosed as osteoarthritis Patients who give a history

of superimposed acute joint symptoms are labeled as type

component are designated as type D Type E (asymptom-

atic), as the name implies, refers to those individuals who have only radiologic evidence of disease, but no

symptoms This variant may be the most frequent of all

T \ p e F (pseudoncuropathic joint) is the rarest 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 The only excep-

tions are those instances when the 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 M t r r l i ~ ~ f r s t t r 1 i o r l s

Rarely, CPPD disease involves the head and 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

thc ear 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 prcs-

ence o f linear punctuate calcitication o f the menisci and

calcitic deposits in the midzone of the hyaline articular

cartilage I n the TMJ the typical appearance is that o f

either a slightly or heavily calcified 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 The CPPD crystals appear in tissue sec-

tions as slightly basophilic rhomboids, cubes or rectangles

and, only rarely, as needles (IS-17; Fig 7) In general

needles if seen at a l l tend to 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 multinucle-

ated giant cell reaction and fibrosis

Tophi similar to those seen in gout may 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 dis-

tinguished from gout This can ltsually 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 diffrac- tion and infrared spectroscopy, can also be used Table I lists the features that are useful in separating the two conditions

Treatment and Prognosis Patients with limited,

asymptomatic disease generally require no treatment Oth- ers however may require ( a ) joint aspiration to remove the crystals (h) colchicine or nonsteroidal anti-intlamma- tory 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), corrcc- tion of the underlying metabolic disorder has not resulted

i n the disappearance of crystallinc deposits (S)

I.D Synovial Chondromatosis Introduction Synovial chondrotnatosis (SC) is a be-

nign condition characterized by the occurrence of meta- plastic 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 Sodium 11rate Calcium pyro-

Shape

Diseases of the Bones and Joints 1059

Primary SC occurs in all age groups (average 40-45

years) and is two to three times more common in males (3-

5) The knee is, by far, the most common location, account-

ing for 70% of all cases, with the second most common lo-

cation being about equally divided between the hip and el-

bow (43) The shoulder, wrist, metacarpal, and

temporomandibular joints are rarely involved The disease

is monoarticular and unilateral in 90% of patients (5)

Secondary synovial chondromatosis is common and,

as the name implies, is always secondary to some other

condition, such as osteochondritis dessicans and the vari-

ous inflammatory and noninflammatory arthropathies The

knee and hip are the preferred sites

Synovial chondromatosis rarely involves the temporoman-

dibular joint ( T M J ) (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 ( 6 0 4 5 % of all cases)

than the left and, in contrast with other sites, affects women

( 5 7 4 7 % 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 preauric- ular mass or swelling, at times associated with pain,

crepitus, clicking sensation on opening the mouth, re- stricted movement of the jaws, 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 Radiographic procedures 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, plain radiographs will be normal (9,11,14- 16) The absence of radiopaque bodies on radiologic examination does not exclude the diagnosis because the appearance of loose bodies varies with the degree of calcification of the cartilaginous nodules In these in- stances, computed tomography (CT) or magnetic reso- nance imaging (MRI) may be helpful

Pathology Miligram recognizes three phases of the

disease: (a) active synovial disease without loose bodies; (b) synovial nodules associated with 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 temporoman- dibular 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

Figure 9 Specimen radiograph of Fig 8 showing pressure erosion

of the underlying bone by synovial chondromatosls

from microscopic to several centimeters (see Fig 8)

The disease begins with the formation of round discrete

cartilaginous islands within the subsynovial connective

tissue, rather than the synovial cells per se (Fig 10) The

chondrocytes are plump, hyperchromatic, and occasion-

ally binucleated As the nodules enlarge, they may undergo

patchy calcification or ossification, lose their synovial

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,

the number of loose bodies has ranged from 1 to 480,

with most cases containing between 15 and 50 (15)

In rare instances, synovial chondromatosis may simul-

taneously coexist with other joint diseases, such as pig-

mented villonodular synovitis and pseudogout (28,29)

Differential Diagnosis Caution must be exercised in

evaluating biopsy specimens of synovial chondromatosis,

because the histological changes, on occasions, are similar

enough to those of chondrosarcoma that they may cause

diagnostic confusion, especially in those few instances

for which the disease extends beyond the joint space (11,17,19,22)

If the disease is clinically and pathologically confined

to the synovium and joint space, rather than bone, then the cytological atypia can usually be ignored Primary chon- drosarcomas of the synovium and chondrosarcomas alleg- edly arising from preexisting synovial chondromatosis are exceptionally rare, but have been described (30-32) Sev- eral 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 adja- cent bone, rather than pressure erosion (30)

Synovial chondromatosis may also extend beyond the

TMJ into the parotid gland and masquerade, on biopsy,

as a pleomorphic adenoma (IO) The presence of an

epithelial component, as seen in a pleomorphic adenoma, readily allows one to distinguish between these two enti- ties

Treatment and Prognosis Because there is no ten-

dency for the disease to resolve spontaneously, treatment

Diseases of the Bones and Joints 1061

consists of surgical removal of the loose bodies and

excising as much of the synovial membrane as possible

(4) Failure to treat can result in secondary degenerative

joint disease For more extensive disease, it may be

necessary to resect the condyle and reconstruct the joint

More recently, there have been attempts to remove the

diseased synovium and loose bodies arthroscopically, a

relatively noninvasive alternative to open arthrotomy

(2,24) However, if the loose bodies are large, they may

not be able to be removed through an arthroscope Radio-

therapy is of no use (4) Local recurrences are infrequent

Figure 10 Low-power magnification

of synovial chondromatosis showmg well-circumscribed nodules of focally

calcified cartilage lying in the subsy- novial connective tissue (H&E, X40)

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 dis- ease The knee and hip are the most common locations, accounting for 70 and 16% respectively, of all cases (2,5) The ankle, foot, wrist, elbow, and shoulder constitute most

of the remaining sites

and are related to the adequacy of the synovectomy

locally aggressive There are rare reports of the disease I Difbse PVNS

extending beyond the TMJ to involve the parotid gland,

external auditory canal, and even the middle cranial fossa

(10,11,17.19,22)

Reports of diffuse PVNS occurring in the temporomandib- ular joint (TMJ) are extremely rare (6-13) Youssef et al reported an example in 1996 and reviewed 16 additional

I.E Pigmented Villonodular Synovitis

Terminology Pigmented villonodular synovitis

(PVNS) is an idiopathic, benign, sometimes locally aggres-

sive inflammatory-proliferative synovial disorder that was

first recognized in the 1850s However, it was Jaffe et al.,

in 1941, who first introduced the term PVNS and defined it

as a clinicopathological entity (1) The disease exists in two

forms: localized and diffuse, with the former accounting

for about 75% of all cases and the latter 25% (2)

The localized variant generally presents as a discrete

mass with a smooth border Although it may involve the

joint space (localized nodular synovitis), most are extra-

articular, with 75-80% arising from tenosynovium of

cases in the literature (1 3) These 17 cases occurred in 5

males and 12 females who ranged in age from 10 to 62 years (average 44 years) The left TMJ was the site of disease in 13 cases and the right in 4

In this area, the disease usually presents as a gradually enlarging, preauricular swelling, occasionally associated with pain on mastication The joint eventually becomes

“stiff” and may limit opening of the oral cavity Some patients have even experienced conductive hearing loss and serous otitis media, presumably from interference with the function of the eustachian tube (10)

On physical examination, the joint may appear swollen (owing to synovial thickening and effusion) and, at times warm, but not necessarily tender In other cases, a discrete,

firm, nonmobile mass may be detected, which is often

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 right conductive-hearing loss associated

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 Radiographic studies show a constel-

lation of findings that may include one or more of the

following: (a) a normal or narrowed joint space, (b)

diffuse thickening of the joint capsule, (c) a localized

intra-articular or para-articular soft-tissue density, with or

without erosion of the adjacent articular cartilage and

bone, and (d) one or 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 examination the synovium ex-

hibits various shades of brown, depending on the hemosid-

erin content, and is diffusely thickened, shaggy and vil-

liform, or nodular Microscopically, elongated papillary

fronds are capped by hyperplastic synovial cells (Fig 12

and 13) The stroma is vascularized and varies from cellu-

lar to collagenous; with areas between these two extremes

The cellular areas are composed of histiocytes (?synovial

Figure 11 An MRI of pigmented villonodular synovitrs of

the left temporomandibular jolnt in a 60-year-old man pres-

enting 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.)

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

PVNS may also be diagnosed by fine-needle aspiration, provided the cytopathologist is provided with sufficient clinical information (20)

Differential Diagnosis The two lesions that are most

often confused with PVNS are malignant fibrous histiocy- toma (MFH) and the central (intraosseous) giant cell

granuloma (CGCG) In contrast with MFH, PVNS usually

does not exhibit a diffuse storiform pattern, 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

Treatment and Prognosis Treatment consists of complete removal, which generally requires a synovec- tomy (2) If the adjacent bone is involved, simple curettage

is usually sufficient, but if extensive, local resection with joint replacement may be necessary Although synovec- tomy removes the disease, some patients may end up with

a less functional joint and greater pain than before the oper- ation (2) Radiation therapy has also been used and may

Diseases of the Bones and Joints 1063

cause regression of the disease, but joint stiffness is a fre-

quent complication In addition, the long-term carcino-

genic potential of such therapy must also be considered

At least 2 of the 17 (12%) cases of diffuse PVNS of the

TMJ reviewed by Youssef et al developed one or more lo-

cal recurrences following attempts at surgical excision

(13) This compares with an average rate of recurrence of

22% (range 1746%) when all joints are considered (2)

Although usually confined to the joint space or imme-

diate para-articular area, diffuse PVNS may be locally ag-

Figure 12 Pigmented villonodular synovitw: Low-power view showing elongated papillary fronds of synovium

(H&E, X 100)

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) Such cases are fortunately rare and do not necessarily indicate malignant transformation

Etiology The etiology of PVNS has been debated

for years and still continues The controversy centers around whether the lesion is reactive, inflammatory, or neoplastic Some believe that PVNS is related to trauma

This theory is diluted somewhat by the fact that only 38%

Figure 13 Pigmented villonodular synovitis: Low-power vlew showing fu- sion of the papillary fronds creating a nodule (H&E, X 100)

Figure 14 Pigmented villonodular

synovitls: Higher power showlng histio-

cytes (?synovial cells) wlth hemosld-

erin foam cells, inflammatory cells,

multlnucleated glant cells and focal fi-

brosls (H&E X200)

of patients can recall a history of trauma (2) Whether the lesion is a neoplasm (24) It is entirely conceivable

chronic, repetitive unperceived, minor trauma is a factor, from the foregoing studies that the etiology of PVNS may

Immunohistochemical studies have provided mixed re-

sults Some indicate that the proliferating mononuclear

cells are of monocyte-histiocyte derivation, whereas oth-

ers suggest that they are of synovial origin (21-23) Ray

I.F Ganglia-Synovial Cysts of the Temporomandibular Joint

et al have identified a clonal abnormality (trisomy 7) in Terminology, Etiology, and Pathology The terms

a single case of PVNS, which supports the contention that ganglion and synovial cyst are often used interchangeably

Figure 15 Collapsed multilocular

ganglion of the right temporomandibu-

lar joint masquerading as a parotld

tumor

Diseases of the Bones and Joints 1065

and are erroneously considered by many to be synony-

mous Although both occur near joints, they differ in origin

and histology Ganglia arise as a result of idiopathic myx-

oid degeneration of para-articular connective tissue (1) As

the thick tenacious, gray-white ground substance accumu-

lates, unilocular or multilocular 1 - to 4-cm cysts are formed

(Fig 15) The cysts are lined only by dense connective tis-

sue, rather than synovium (Fig 16) Consequently, they are

pseudocysts rather than true cysts They may have an at-

tachment to the articular capsule, but rarely, if ever, com-

municate with the joint space Synovial cysts, on the other

hand, are true cysts lined by synovial cells and may or may

not communicate with the joint cavity (2) They arise from

herniated articular synovium, adventitial bursa, or tenosy-

novium Whether trauma is an important event in the for-

mation of some ganglia or synovial cysts is uncertain

Clinical Features Although the vast majority of gan-

glia 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 features of 14 such

cases are summarized in Table 2 Analysis of this data

indicates that G-SC are more common in women (79%

of all cases), affect both joints about equally and have

thus far been described only in adults from 22 to 64 years

of age (average 42 years)

Although typically unilateral and juxta-articular, Farole

and Johnson reported a patient who had bilateral, synchro-

nous G-SC of the TMJ (14) Pate1 et al described another

Figure 16 Ganglion of temporoman- dibular Jolnt shown in Fig 15: Note that it is lined by only connective tissue, not epithelium; therefore, it is a pseu- docyst and not a true cyst (H&E,

x 200)

patient who had an intraosseous G-SC of the mandibular condyle, with no evidence of predisposing degenerative joint disease (6)

A G-SC of the TMJ characteristically presents as a painless, slowly enlarging, soft-to-firm, preauricular mass that does not interfere with movement of the jaws or cause facial nerve dysfunction A few individuals, however, have complained of pain, especially on direct pressure Others have experienced a “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 erosion of adjacent bone

is not uncommon

Treatment and Prognosis Surgical excision is the treatment of choice Because G-SC are rarely suspected clinically, both the patient and surgeon are mentally pre- pared for removal of a suspected deep lobe parotid tumor There are, however, some clues that should suggest a G-

SC In addition to its cystic appearance and para-articular location, G-SC tend to be located at the superior border

of the parotid gland (high preauricular area) and often decrease in size when the mouth is opened, owing to 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 physical manipulation, and are located at the angle of the mandible (15)

Follow-up and long-term prognosis on G-SC of the TMJ are virtually nonexistent The only exception is the

Table 2 Clinical Features of Ganglia and Synovial Cysts o f the Telnporomandibular Joint

on touching or opening the mouth

tion on opening jaws

opening J W S

pain on palpation or movement ofjaws

satton when mouth was opened widely

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

case of Shiba et a l ( I O ) In this instance, the lesion was

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

to the extravasated fluid The incidence of recurrence

following surgical excision of G-SC i n other sites has

ranged from 17-31% ( I )

11 NONNEOPLASTIC DISEASES OF BONE

AND JOINTS

1I.A Osteomyelitis of the Jaws

Osteomyelitis of the jaws can develop under a variety of

conditions, the most 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~rtc S ~ ~ p p r r ( r t i \ ~ Ostcwrr~yditis

Etiology and Pathogenesis Acute osteomyelitis in-

volves 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 tuberculo-

sis, and actinomycosis ( 2 ) Alternatively, acute osteomyeli-

tis Inay develop following the entry ofpyogenic organisms

subsequent to fractures or penetrating wounds (2.3) How-

ever, i n Western countries, most cases in the adult are asso- ciated with an infected postextraction alveolus or a pcriapi- cal lesion (abscess, granuloma, or cyst) 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 re- sults in gangrenous necrosis of the orofacial tissues), acute necrotizing ulcerative gingivitis and periodontal disease

are additional important etiologic factors ( 3 ) A local in-

flammatory state caused by bacterial infection leads to mi- crothrotnbotic events (7) This results i n a defective micro- circulation 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 s was the usual caus- ative organism (1.4) More recent studies have demon-

strated that most infections arc polymicrobial with Sfrup-

t o c o ( ~ ~ 1 1 s ~ r ~ ~ 1 0 1 ~ e ~ ~ ~ i I I ~ r s ~ Elrhcrc.terilrtrr Klohsiellu and Bcrctc~roit1c.s species 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 in- creased number of anaerobes also play an important ctio-

logic role (S.9,lO) Other frequently cultured bacteria in- clude S ~rlrrms, Esc~hcrichitr coli, Willorrelltr p r r ~ w l ~ r ,

Diseases of the Hones and Joints 1067

F ~ r s o b r r ~ t c ~ r - i l r r ~ ~ nucler1tur11, and P r l , t o s t r ~ ~ ~ t o c o c ~ ~ ~ s r q q -

t1ll.S (S)

With the advent of antibiotics most periapical infec-

tions rarely proceed to an acute osteomyelitis in healthy

persons On the 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 inlmuno-

suppression, 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 osteomy-

elitis (6)

Dental infection is less likely to be the source of

ostemyelitis during childhood (IS) Instead, direct spread

from an otitis media or nlastoid infection or hematoge-

nous dissemination of infections from elsewhere in the

body, accounts for many cases (2.12 IS) The factors

that determine the development o f osteomyelitis and its

progress in both children and adults include ( a ) the viru-

lence 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 inflamma-

tory process spreads so quickly through the medullary

spaces that there is insufficient time for the body to react

to the infiltrate (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 ' con-

junction with Paget's disease osteopetrosis, or advanced

cemento-osseous dysplasia, hypoxia induced by compro-

mise of the blood vessels is the initiating, rather than

consequential, event Because the pathogenesis of the

osteomyelitis associated with these latter disorders thus

differs from that related to the other causes identified i n

the foregoing, i t is n o t included in this section

Clinical Features Acute osteomyelitis can occur in

dentulous and edentulous areas (S) The mandible gener-

ally the body is affected more commonly than the maxilla

(S) The rarity of maxillary osteomyelitis has been as-

cribed to its more profuse blood supply (2.3.18) Lesions

of the mandible are encountered most frequently in the

third decade of life (3) Maxillary disease on the other

hand demonstrates a higher incidence i n pediatric popula-

tions and often evolves as ;I consequence of cancrum oris

and acute ulcerative gingivitis (3.19)

In either location, the disease is manifest by severe

pain, fever chills regional lymphadenopathy leukocyto-

sis erythema or swelling sinus formation and a purulent

discharge (3.S,6,I6.17,19) Pathological fractures and se-

questrum formation occur less frequently (3.S), with the latter exhibiting a higher frequency in the maxilla (3) Sequestra often exhibit spontaneous exfoliation (16) Par- esthesia and anesthesia are sometimes experienced, partic- ularly if the mandible is the site of infection (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 must be lost before changes can be recognized (6) Therefore, the

radiographs may appear virtually normal until the osteo- myelitis has been present for at least 7-10 days from the onset of symptoms (12.20) At that time 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 involve- ment Inay even precede clinical manifestations (23.24) and herald the presence of osteomyelitis before osseous changes are apparent on plain radiographs (25) Despite this sensitivity, reports of false-negative results with tech- netium (Tc) scanning have appeared (26) Therefore, when 9y'11Tc scan is nondiagnostic, but osteomyelitis is still suspected clinically, a gallium 67 citrate scan can be performed to confirm or exclude the presence of the 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 infiltrated with

numerous neutrophils (see Fig 17A) Eventually the adj,- cent trabeculae of bone lose their viability and demon- strate ragged areas of resorption a loss of their peripheral border of osteoblasts, and a disappearance of osteocytes from the lacunae Necrotic debris and bacterial coloniza- tion may also be apparent

Treatment and Prognosis In all instances malnutri-

t i o n if present, should be corrected and a l l associated

Figure 17 Acute suppurative osteomyelitis: (A) Numerous intact

and degenerating neutrophils are present in the medullary space

(H&E, X 200) (B) The trabecular pattern is indistinct and seques-

trum formation 1s evident (arrow) (B, courtesy of M El-Attar,

Unlverslty of Pittsburgh School of Dental Medicine, Pittsburgh,

PA.)

debilitating diseases must be treated (3) Conservative

management of the osteomyelitis itself consists of drainage

and the administration of appropriate antibiotics, as deter-

(3,5,16,30) The exact duration of antibiotic treatment re-

quired is difficult to establish, and the recommended time

has ranged from 2 weeks to 6 months (5,12,31) A variety

of antibiotics have been employed, the advantages and dis-

advantages of which have been discussed by Ord and El

Attar (1 2) Calhoun et al (5) found no significant differ-

ences in cure rate based on the choice of antibiotics, num-

ber of antibiotics, or duration of antibiotic administration

Davies and Cam recommend that patients with a history of

alcohol abuse be premedicated with antibiotics before any

dental extractions because these individuals are more prone

to infection Furthermore, the response to the osteomyelitis

in this instance may be attenuated so that the diagnosis is

delayed until the infection is advanced (6)

The development of sequestra is frequently encoun- tered When small, these may be exfoliated spontaneously Some authors recommend sequestrectomy for larger ones (3,5,12), whereas others have concluded that this proce- dure is not necessary in all cases because, under favorable

circumstances, even fairly large sequestra can be rendered sterile by antibiotic therapy (4) Other types of surgical procedures that have been used include complete removal

of diseased bone, tooth extraction, and fracture fixation ( 3 3 , as well as decortication and resection (3,6) Tooth extraction is limited to those teeth that have lost their bony support, and it is carried out in conjunction with

Diseases of the Bones and Joints 1069

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) i t is followed by the placement of an iliac bone

or rib graft (4) The combination of antibiotics with

metronidazole which is particularly effective against aero-

bic organisms, has been quite useful (3) A system con-

sisting of the use of surgical intervention and antibiotic

treatment based on the stage of the disease (degree o f

bone involvement) after correction of any underlying

systemic disorder has been 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 been useful when used in

patients with underlying medical problems and in those

i n whom other forms of treatment have failed (S) How-

ever, 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

Differential Diagnosis Distinction should be made

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 S infection of the midface during the first weeks of

life Comprehensive descriptions and reviews of the vari-

ous features of this disorder have been presented by

several authors (33.35-5 I ) The child develops restless-

ness and fever, followed by cdetna and erythema of the

periorbital region and eyelids Chemosis and cot1.junctivitis

are common, and exophthalmos or 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

which is increased by pressure on the bulbus oculi, be-

comes evident The palatal mucosa on the affected side

becomes bright red and is pathognomonically sharply

demarcated from the normal side by the median raphe

Abscess formation, sinus tract development a suppurative

discharge sequestration of tooth germs and the establish-

ment of an oral-nasal fistula follow soon thereafter Nccro-

sis of tooth germs takes place and is reflected by hypoplas-

tic 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 organ- ism 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 on the hands of attending nurses, have been proposed A break in the oral mucous membranes would permit bacterial invasion of the jaw, with subsequent spread to the orbit through the tooth germs Alternative possibilities include extension from the nose or lacrimal duct into the 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 support- ive 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

Etiology and Pathogenesis This form of ostcomy- elitis may develop de novo or following the subsidence

of the acute phase of the disease For inclusion i n the latter category, the lesion must be of at least 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 micro- organisms have been found to be a predominant etiologic agent (19)

I n chronic suppurative osteomyelitis thc host's re-

sponse to infection results in the production of highly vnsculnr granulation tissue that is 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 a s bacterial reservoirs This results in

a persistent focus of infection that is prone 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)

Clinical Features The highest frequency is i n the body and angle of the 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 study of

23 cases, 65% occurred in the sixth through the eighth decades ( 14) The age varies from I3 to 88 years ( 14.19) with the mean falling in the fifth (19.45) or sixth (14) decade

Swelling pain and draining fistulae constitute the most common manifestations Symptoms of acute disease such

as fever and leukocytosis, are typically absent (19) De-

struction 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 radio-

paque areas, thus imparting a “moth-eaten” appearance

(16,46) Sequestra are likely to be present (16,21) Occa-

sionally the surrounding bone exhibits an increased den-

sity, and the cortical surface may exhibit a periosteal

reaction ( 1 6) Magnetic resonance imaging (MRI) is valu-

able in evaluating residual areas of infection and in provid-

ing detailed information concerning the extent of involve-

ment 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

the fibrotic marrow Irregular bony trabeculae may be

present, together with occasional osteoclasts and osteo-

blasts 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 man-

agement 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

with the use of appropriate antibiotics (4,5,16,19,30,47-

49) In small lesions curettage, sequestration, and saucer-

ization constitute the usual mode of treatment When

larger segments of bone are involved, decortication or

saucerization are often used, together with the transplanta-

tion 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 within the microcirculation, and (b) obstruc-

tion 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 con-

comitantly with heparin can overcome the problems of

drug delivery introduced by activation of the blood coagu-

lation and fibrinolysis system (44) Furthermore, the direct

insertion of polymethylmethacrylate beads impregnated with gentamicin (S 1-53) or tobramycin (50,S4) produces high concentrations of antibiotics in a localized site with- out 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 and renal 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 conjunc- tion with antibiotics or antibiotics and surgery vary from demonstrating a marked improvement to a complete cure

An MRI scan is useful in guiding surgical debridement because of its ability to differentiate between active in- flammation and chronic fibrosis and to detect noncontigu- ous areas of involvement (2 1.61 ) Scintigraphy ( 1 6 3 9 ) and repeated measurements of serum levels of CUI -anti- trypsin, orosomucoid, and haptoglobin (62) can also be used to follow the progress of treatment The synthesis

of these particular proteins in the liver is regulated by inflammatory mediators, such as interleukin- 1 , interleu- kin-6, tumor necrosis factor prostaglandin E,, and leuko- triens in the affected areas (62)

( 1 2,30,58-60)

Etiology and Pathogenesis Chronic focal sclerosing

osteomyelitis (CFSO), also referred to as condensing oste- itis, represents a hyperplastic reaction of bone to a mild bacterial infection ( I ) The ensuing sclerotic bone arises as

a consequence of excessive apposition o f the bone trabecu- lae 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 resto- ration ( 1,3) or, less frequently, a cracked tooth (4)

Clinical Features CFSO has been seen in about 7- 8% 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 others have 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 than mild pain related to the infected pulp, there are generally no signs or symptoms associated with this condition (1,4) As a reflection of the

Diseases of the Bones and Joints 1071

pulpal necrosis, the affected tooth does not respond to

vitality tests

Radiography CFSO presents as a radiopaque peria-

pical mass of sclerotic bone The borders of the lesion

may be smooth and well-defined, or appear to blend into

the surrounding bone (Fig 18A) The adjacent tooth

exhibits a continuous, often thickened periodontal liga-

ment and, sometimes, a concurrent apical inflammatory

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 may not be

bordered by osteoblasts, depending on the degree of activ-

ity present at the time of evaluation The intervening soft

tissue, if present, is usually fibrotic and is occasionally

infiltrated by scattered lymphocytes (1; see Fig 18B)

Treatment and Prognosis Management entails ei-

ther extraction or endodontic therapy of the involved tooth

In endodontically treated teeth, regression of the lesion ac-

companied by normalization of the periodontal ligament

has been noted in 85% of cases (3) In some instances, re-

modeling does not take place, even following extraction

Figure 18 Chronic focal sclerosing osteomyelitis: (A) A well-

defined radiopaque mass (arrow) is present adjacent to the apices

of the mandibular first molar (B) Histologically, the lesion consists

of a dense mass of bony trabeculae and intervening fibrous 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.)

and thus may persist radiographically for an indefinite pe- riod (7,12; Fig 19) This residual area of sclerosis is re- ferred to as a bone scar (1 1) Its surgical removal is not re- quired unless it becomes symptomatic (1)

Differential Diagnosis Radiographically, CFSO

must be distinguished from a cementoblastoma, hyperce- mentosis, periapical cementa1 dysplasia, focal cemento- osseous dysplasia, and an ossifying fibroma (10) The criteria used for accomplishing these distinctions have been discussed in other sections of this text Focal periapi- cal 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 Sclerosing Osteomyelitis

Chronic diffuse sclerosing osteomyelitis (CDSO) is a poorly understood disease that differs from the usual form

Figure 19 A residual area of chronic focal sclerosing osteomy-

elitis (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 non-

suppurative osteomyelitis (1) or osteomyelitis sicca (2)

Etiology and Pathogenesis The fundamental nature

of CDSO is unclear, and the literature is replete with

conflicting philosophies and terminology Although infec-

tion, probably of dental origin (periodontitis; pericoronitis,

periapical inflammatory disease) has been the predominant

consideration ( l ,3-5), there has been considerable diffi-

culty in substantiating this concept owing to the inability

to consistently isolate a noncontaminant, causative micro-

organism from the lesion However, as a result of the

success of their more stringent techniques, Marx et al (6)

have presented evidence to support the contention that

CDSO represents a specific infection produced by Actino-

anaerobic pathogens, of which Eikenella corrodens is the

most common The resultant disease is nonsuppurative

and produces an endosteal and periosteal sclerosis of the

or bone ischemia (6,7) Other proposed possibilities in-

clude reactive hyperplasia of bone (8), painful fibro-

osseous disease related to fibrous dysplasia (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 tendoper- iostitis that develops in response to overuse of the masse- ter 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

Diseases of the Bones and Joints 1073

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 col-

leagues (3.4,7,15-17), as well ;IS by Schneider and Mesa

( 1 8) Tsuchimichi et a l ( I O ) , and Marx et a l (6)

Clinical Features CDSO is characterized by a local-

ized swelling and repeated eplsodes of pain, both of which

arc unilateral and restricted to the mandible Swelling

along the lower border of the mandible owing to high

periosteal reactivity is ;I prominent feature in the carly

stages, particularly among younger patients Exnccrba-

tions occur at intervals that vary from months to years

and generally last for 1-3- weeks The episodes o f pain

are more frequent and more severe i n 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 on the temporoman-

dibular 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 sedimen-

tation rate has been elevated during periods of exacerbn-

tion, but other laboratory tindings are within normal limits

The disease can appear at any age but is most common

i n young adults, the mean 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 lesion is not restricted

t o the tooth-bearing parts of the mandible but can extend

from the alveolar ridge t o the inferior border and can

affect the ascending ramus, including the condylar pro-

cess 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 corrc-

spond well with osteolytic areas Scintogrnphy is a valu-

able 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 nar-

rowed haversian canals and ;I mosaic pattern indicative

of previous remodeling these features arc seen in the

peripheral parts of the lesion (h) Coarse irregular bony trabeculae, with fibrotic marrow spaces containing scat- tered lylnphocytes and plasma cells; multinucleated ostco- clasts are present along the borders o f thc trabeculae:

markedly widened blood vessels are see11 adjacent t o amorphous, necrotic or osteoid areas; this entire second pattern constitutes the most characteristic changes associ- ated 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 cxhib- iting abundant perivascular lymphocytes and plasma cells

as well as osteocI;1sts: this pattern is sometimes seen in the deepest parts of the lesion

Although these features may be characteristic they are nonspecitic and often subtle Consequently it must be emphasized that a definitive diagnosis requires the integra- tion of pathological findings into information derived from clinical and radiographic assessn1ents

Treatment and Prognosis 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 can be a serious debilitating disease that, i n some instances, has led to narcotic addiction or emotional disturbances (6) Spontaneous remissions are infrequent Factors that have been 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 oc- curring during the periods of acute exacerbations olicn with only minimal success in alleviating discomfort or prc- venting their subsequent reappearance These include the use of antibiotics, hyperbaric oxygenation radiation thcr- apy, analgesics and sedatives and removal of infectious foci and sequestra (3,23 25) Severe cases have bcen treated by decortication o r resection o f the affected areas (9,26-29) The success rate lollowing decortication is ap-

proximately 50% (O,29) I n most instances of failure, symptoms recur within I year postoperatively Sex, loca- tion, 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 im- provement are significantly older a t the onset of symptoms and at the time of surgery, are considerably more likely to

be edentulous (29) Resection of the affected area may cre-

ate various postoperative complications, such as loss of

function of the inferior alveolar nerve and problems associ-

ated with mandibular reconstruction Consequently, resec-

tion should be restricted to severe, therapy-resistant pa-

tients Repeat decortication to cover a larger area and

extraction of nonvital teeth is preferred over resection (29)

Jacobsson and Hollender have conducted a comprehen-

sive analysis of the efficacy of various therapeutic modal-

ities (3) From their observations, they have formulated

thc following recommendations: (a) treatment should be

initiated with penicillin, even if cultures are negative,

and continued for at least 3 months, unless a culture or

sensitivity test shows that another type of antibiotic would

be more favorable: (h) if antiphlogistics are unable t o

suppress pain and swelling, cortisone therapy should be

given; (c) the patient should be kept under observation

for several years; (d) stretch exercises in patients with

trismus should be avoided, and tooth extractions should

be performed only when absolutely necessary and under

antibiotic coverage Failure to do so may accelerate the

endosteal spread of CDSO Furthermore, Bell has recom-

mended the use of a surgical approach, with removal of

adequate amounts of bone to facilitate delivery of the

tooth and to increase bleeding (30); (e) decortication may

be employed if the initial treatment fails and the clinical

symptoms and radiographic changes continue to progress;

( f ) cortisone is advocated in late chronic stages for which

the effect of antibiotics is qucstionable; and (g) radiation

therapy should be avoided because of the risk of late

complications, particularly a malignancy (3)

Gallium-67 citrate is highly useful i n evaluating the

response to treatment (31.32) It is also effective as an

adjunct to technetium-99m imaging in the identification

of continuing or recurrent sepsis and in the more precise

localization of the focus of infection (33) This latter

agent, used alone however, is less valuable for monitoring

therapy (19) because i t continues to accumulate in healing

bone as a result of increased remodeling activity (32),

thus producing a scintigraphic abnormality that can persist

for up to 6 months after clinical recovery (34)

Differential Diagnosis The condition most often

confused with CDSO is florid cemento-osseous dysplasia

The characteristics that differentiate between these two

entities are shown in Table 8 of this chapter Other lesions

that should should be included in a differential diagnosis

are proliferative periostitis (see immediately following

paragraphs), fibrous dysplasia, Paget’s disease, and malig-

nant tumors of bone (7), the essential contrasting features

of which are summarized in Table 3 A more complete

discussion of these diseases can be found in various

sections of this chapter

Table 3 Differential Diagnosis of Chronic Diffuse Sclerosing

Osteomyelitis Diagnosis Characteristics

Florid cenlento-osseous dysplasia

Proliferative periostitis

Fibrous dysplasia

Paget‘s disease

Malignant tumors of hone

See Table 8 i n thls chapter Occurs mainly in children as well

as young adults; frequently a s -

sociated with a carious tooth Deposition of bone is confined to the outcr surface of thc cortex:

High alkaline phosphatase activ- ity found in libroblast-like cells

Occurs mostly in older patients and more often in males: not restricted to mandible or unilat- eral locat~on: increased serum alkaline phosphatase

Cotton wool appearance and hyp- erccmentosls

No tissue necrosis

Often accornpanled by paresthe- sis, loosening of teeth ulcer- ation, and bleeding Biopsy re-

quired for definitive diagnosis

ll.A.5 Prolifircrtiw Periostitis

Proliferative periostitis (PP) or periostitis ossificans repre- sents a hyperplastic periosteal reaction to inflammation The eponym “Garfe’s osteomyelitis” has also been used as

an alternative designation for this condition However, this term is now deemed inappropriate because, a s pointed out

by Wood et al., Carte’s original report made no mention of periostitis, no pathological specimens had been available for examination, and X-rays had not as yet been discovered ( I ) Several isolated examples of this disorder have ap- peared in thc dental literature The most comprehensive re- views and analyses of PP of the jaws have been those of Eversole et al in 1979 (2) and Nortje et al in 1988 ( 3 )

Etiology and Pathogenesis The evolution of PP entails the spread of infection and an inflammatory rc- sponse through the buccal cortical plate with the resultant

Diseases of the Bones and Joints 1075

stimulation of the periosteum to deposit new bone (3-5)

The affected periosteum forms several rows of reactive

bone that parallel each other and expand the surface of

the altered bone (6) The most common source of the

initiating factors is periapical inflammatory disease that

develops secondary to caries-induced pulpal necrosis

(2,3,5-18) Other odontogenic and nonodontogenic in-

flammatory stimuli can also trigger the requisite periosteal

irritation These include pericoronitis (i.e., inflammation

of the mucosal flap that covers a portion of the crown of

a partially erupted third molar); a periodontal defect; an

infected mandibular buccal or dentigerous cyst, trauma,

congenital syphilis, tonsillitis, primary tuberculosis of the

mandible; pharyngitis; and a parotid abscess (2,3,6,

8,10,12,15,19-24) However, in some instances, the under-

lying cause cannot be identified (2,3,13-15,20,25-27)

Clinical Features Typically, the patient presents

with facial swelling associated with a bony hard enlarge-

ment of the mandible The lesion may be asymptomatic

or accompanied by mild to moderate pain that may be per-

sistent or episodic (2,5,7,8,1&12,14-16,20,23,26,28,29)

(Fig 20A) Jaw movements may be restricted to a varying

extent (8,13,17) Malaise and lymphadenopathy have also

been noted (17) The most common site of the periostitis

is the inferior border of the posterior mandible, followed

by the buccal aspect and, finally, the lingual aspect (3) Rare instances of association with the sigmoid notch area

and maxilla (3), as well as the ramus and coronoid process (23) have also been noted With the exception of the unusual case described by Eisenbud et al (27), in whom all four quadrants were affected, the osseous involvement

is unilateral (2,3) The offending tooth in most patients is the mandibular first molar (3) The overlying skin and mucous membrane are usually, but not always (8), normal

in color and texture (5,7,8,11,12,20,25,28) Afistula on the skin has been reported in one instance (9) The simultane- ous occurrence of a central giant cell granuloma has been described by Toller and Karaca (29) Although an increased erythrocyte sedimentation rate has been reported in one pa- tient (27), the laboratory values in PP are generally noncon- tributory (25,30) Results of microbial cultures are often

negative as well (1 2)

In the 93 examples reviewed by Nortje et al (3), the

age of the patients at the time of presentation ranged from

2 years to 69 years (mean, 13.3 years) Eighty-five (93%)

of these individuals were of mixed race with the remainder being equally divided between white and black There was only a slight male preponderance (1.27: 1)

Radiography The predominant radiographic ap-

pearance is one of cortical duplication or onion-skinning

(2,3,5-7,11,12,15,20), which probably results from pro-

gressive exacerbation and remission of the infection (3;

see Fig 20B) The periosteal reaction may appear as a

single layer or multiple layers (3) Importantly, the original

cortex remains well-defined (2,3) Less frequently, subper-

iosteal tumescence is encountered, characterized by a

mottled radiolucent-radiopaque pattern (2,27) In either

event, the external border of the affected area is usually

regular and well-delineated (7,28) Another sign often

present is an area of patchy, increased density overlying

the mandible in cases involving the buccal cortex This

increased density is the result of attenuation of the X-ray

beams by the reactive buccal bone as they traverse the

multiple layers (3) Sequestra formation and effacement

of follicular cortices of adjacent unerupted teeth can be

additional findings (3) The best views for visualization of

the periosteal bone are the panoramic and lateral oblique

projections If the reaction is not seen on lateral radio-

graphs, occlusal films should be taken Occasionally, only

a posteroanterior view will adequately demonstrate the

presence of PP (3) Computed tomography is also useful

in establishing the diagnosis, owing to its convenience,

good overview, and sensitivity for both bone and soft-

tissue detail (23) A sunburst pattern has been described

for PP disclosed by this technique and an intense uptake

of technetium-99m methylene diphosphonate has been

demonstrated on bone scintography (26) Panorex or in-

traoral films will often show one or several periapical

radiolucencies of the offending tooth (5,7,11,12)

Pathology The lesion characteristically consists of

trabeculae of bone that are arranged in a linear, parallel

orientation (2.12,28) Alternatively, the trabeculae exhibit

a retiform or fibrous dysplasia-like pattern (2) The in- tervening stroma is composed of fibrous connective tissue generally devoid of inflammatory cells or only sparsely infiltrated with lymphocytes and plasma cells (2.15,16; Fig 21) Sequestra, if included, demonstrate typical fea- tures of necrotic bone (6)

Treatment and Prognosis Treatment consists of ex-

traction or endodontic therapy of the carious tooth, or

removal of other causative factors, often augmented by the administration of antibiotics Gradual remodeling of the jaw subsequently occurs and facial symmetry is re- stored (2,3,12,15,17,26,30) No surgical intervention

is required for the periosteal lesion (2,3,12,26) A biopsy

is unnecessary unless (a) the radiographs demonstrate

a destruction of the former cortical boundary and de- struction within the periosteal new bone, because both

of these signs may be indicative of a malignancy (3,

31,32); (b) movement of teeth or tooth buds are seen (3);

or (c) no obvious source of inflammation can be identified

(6)

Differential Diagnosis Noninvolvement of the end-

osteum in PP is an important radiographic feature that assists in distinguishing it from other fibro-osseous le- sions, such as fibrous dysplasia or ossifying fibroma (2)

Although subpenosteal bone deposition is the preeminent feature of PP, it is not unique to this disorder A similar phenomenon is an integral component of various other developmental, metabolic, reactive, inflammatory, and neoplastic diseases of bone, some of which also affect the jaws A listing of the various neoperiostoses, the distinguishing characteristics of which are discussed in detail by Eversole et al (2) are shown in Table 4

Figure 21 Proliferative periostitis: Parallel, linear

bony trabeculae are embedded I n an intervening stroma

composed of fibrous connectwe tissue that exhibits a

paucity of inflammatory cells (H&E, X 100)

Diseases of the Bones and Joints 1077

11.B Osteoradionecrosis

Osteoradionecrosis (ORN) is one of the most serious and

feared complications of radiation therapy for malignant

tumors of the head and neck, with a reported frequency

of 1-35% ( 1-9) This wide range i n incidence partly

relates to lack of precise criteria for diagnosis Some apply

the term rather loosely to any exposed bone following

radiation Others are quick t o point out that radiation

therapy often results i n soft-tissue necrosis, with or with-

out exposure of bone To qualify as ORN Marx and

Johnson insist that the exposed, irradiated bone be nonvia-

ble and that i t fails to heal without intervention (4) With

this morc rigid definition the reported incidence of ORN

i n most series ranges from 2.7 to 19.1% (l.2.S.6)

For a long time, ORN was thought to be a form of

osteomyelitis Marx, however redefined the concept of

ORN and stated that i t is not a primary infection o f bone,

but rather, ;I radiation-induced, wound-healing defect

characterized by ;I specific pathophysiological sequence

This sequence consists of radiation followed by the devel-

opment of hypovascular-hypocellular-hypoxic tissue and

finally, ;I nonhealing wound that later may or may n o t become infected (3)

Clinically ORN is associated with neurological symp- toms of pain, dysesthesia or anesthesia and is accompa- nied by fetor oris, dysgeusia, and food itnpaction in the area of the exposed tissue Progression may lead

to pathological fractures fistulas, trismus difficulty i n mastication and swallowing and local, regional, or sys- temic infection

Radiologic studies typically show an irregular area of radiolucent bone destruction with areas of radiopacity in- dicative of sequestrum fortnation A pathological fracture may also be seen I t may be difticult or impossible t o distin- guish these changes from recurrent or persistent cancer Pathologically, ORN consists of six basic processes that occur i n the following sequence: hypcremia, inflammation (endarteritis), thrombosis cellular loss, hypovasculnrity and fibrosis (4) The loss of blood vessels and fibrosis, which leads to tissue devitalization, usually appears about

6 months after radiation and becomes progressively worse (4)

Although any bone may be affected, the mandible is

by far, the most frequent site of occurrence i n the head and neck The susceptibility of the mandible over the maxilla is allegedly due t o its smaller blood supply and its more compact bone composition (9)

ORN is most often related to external-beam radiation, because this is the predominant means i n which radiation therapy is delivered to malignant tumors The most severe cases, however, are due to the use of radioactive implants (4,9)

This disorder may o c c ~ ~ r spontaneously ( 1 I-S6% of a l l cases), or it may be related to trautna (44-89% of all cases) (4.6,9) Trauma-induced ORN is most often due t o

dental extractions usually after radiation but sometimes before Other causes include surgical procedures and irri- tation from dentures or other prosthetic devices Marx and Johnson have observed that most spontaneous cases occur

ORN exhibits ;I bimodal peak The first peak develops i n the first 3 months of radiation whereas the second peak appears 2-5 years after exposure (4)

ORN is related t o the dose of radiation dental status of the patient and the anatomical site of tumor The greater the dosage the greater the chance of ORN It rarely devel- ops however, i n doses of less than S 0 0 0 cGy It is also

more likely to occur in dentulous than i n endentulous pa- tients and especially those with poor oral hygiene I t is also

more often seen i n patients with malignancies of the tongue, floor of mouth, and retromolar trigone

The incidence of ORN may be reduced by extracting teeth before radiation Radiation not only damages the

pulp of teeth, but also results in loss of saliva and its

anticariogenic effect Accordingly, it is recommended by

most authorities that all teeth in the area of radiation be

removed and especially so if the dose of radiation will

exceed 6000 cGy Some, however, may permit the patient

to retain their teeth if there is excellent dental health and

assured compliance with frequent fluoride applications If

the teeth are to be removed, radiation should be deferred

for at least 2.1 days to allow adequate healing (4)

Once ORN develops, treatment usually consists of

surgical removal of the dead bone and surrounding tissue,

hyperbaric oxygen therapy, analgesics, and antibiotic ther-

apy (4,s) Although there are reports of ORN being treated

conservatively with antiseptic solutions, it is doubtful

whether these patients actually have ORN as defined

above by Marx and Johnson (4,9)

1I.C Relapsing Polychondritis

Clinical Features Relapsing polychondritis (RPC)

is a rare disorder of unknown etiology characterized by

recurrent episodes of inflammation and degeneration o f

cartilaginous tissues throughout the body, resulting in pain

and deformity of the external ears, nose, hearing loss,

hoarseness, tracheobronchial collapse, arthropathy, fever,

and malaise (1-12) Noncartilaginous tissues, such as the

eyes, heart, and aorta may also be involved

Relapsing polychondritis occurs in all races, affects

both sexes equally, and has been described in individuals

from birth to the ninth decade of life (mean age 4 0 4 5

years; 4,s) Although sporadic cases exist of which more

than one family member or relative have been affected,

there is still no convincing hereditary or familial predispo-

sition (4.13)

The severity of the disease is highly variable Some

patients experience several episodes of chondritis per

month, whereas others may have only one every few

years (2) Each attack typically lasts from a few days to

several weeks before it spontaneously resolves Eventu-

ally, the cartilage is destroyed, resulting in such deformi-

ties as “cauliflower ears” and “saddle nose.” The most

common presenting signs and symptoms, in descending

order of frequency, are auricular chondritis, arthritis, respi-

ratory tract involvement, ocular inflammation, nasal chon-

dritis, and audiovestibular disturbances ( 5 )

The auricular chondritis, which may be unilateral or

bilateral develops rather suddenly and, with the exception

of the lobule, which is devoid of cartilage, involves the

ear diffusely The pinna is swollen, warm, red to vio-

laceous, and tender to touch The pain may be so exquisite

that it interferes with sleep owing to inability to rest the ear on the pillow At times, a clear serous fluid may exude from the ear and mimic an infectious process Hearing loss, which may be conductive, sensorineural, or mixed,

is related to one or more of the following: (a) inflammation

of the cartilaginous portion of the eustachian tube with secondary serous otitis media, (b) suppurative otitis media, (c) swelling, stenosis or both of the external auditory canal, and (d) inflammatory involvement of the internal auditory artery or its cochlear branch (4,6)

Nasal chondritis, similar that of the ear, presents as an area of painful, acutc inflammation Crusting of the nasal mucosa, with intermittent epistaxis may occur, but the latter is not especially common Involvement of the carti- lage of the larynx, trachea, and bronchi typically results

i n hoarseness, tenderness of these structures, recurrent bouts of pneumonia, and varying degrees of airway ob- struction, the latter sometimes necessitating tracheostomy Ocular manifestations include episcleritis, scleritis, iritis, uveitis, conjunctivitis, or keratitis

The arthritis of RPC may be monarticular or polyarticu- lar and involves the large and small joints of both the upper and lower extremities Costochondral, sternomanu- brial, and sternoclavicular arthritis are especially charac- teristic The arthritis may be associated with an effusion but, in general, tends not to be symmetrical or exception- ally deforming

Aortic insufficiency and aortic aneurysms have been observed in 5-10 and 4% of patients, respectively ( 3 3 )

In addition, 2S-30% of persons with RPC suffer from other rheumatic (rheumatoid arthritis, lupus, scleroderma,

or other) or autoimmune diseases (thyroid disorders, ulcer- ative colitis, glomerulonephritis, and such) (5)

There are no laboratory tests diagnostic of RPC The most prevalent abnormalities are an elevated erythrocyte sedimentation rate, anemia, and leukocytosis Results of tests for rheumatoid factor and antinuclear antibodies are positive in about 10-20% of individuals (4,6); however, titers of these antibodies, with the exception of those patients who have other coexistent rheumatoid or autoim- mune disorders, are always low Radiographic studies may show articular cartilage destruction (40%), calcification

of the ears (40%), or tracheal narrowing (32%) (1) The diagnosis of RPC can be made if three or more of the following criteria are present, in conjunction with appropriate biopsy findings: (a) bilateral auricular chon- dritis, (b) nonerosive, seronegative inflammatory arthritis, (c) nasal chondritis, (d) ocular inflammation, (e) respira- tory tract chondritis and (f) audiovestibular disease (S) Etiology The etiology of RPC is unclear Much spec-

ulation, however, has centered around immune processes, but whether they are the cause or the result of the disease

Diseases of the Bones and Joints 1079

is conjectural Attempts to demonstrate serum anticartilag-

inous antibodies in the past have had inconsistent results

(l,3) More recent studies, however, suggest that they are

the rule, rather than the exception (14)

Direct immunofluorescent examinations of ear biopsy

specimens have revealed various combinations of IgG,

IgA IgM and C3 along the chondrofibrous interface (13)

Foidart et al have demonstrated antibodies to type I1

collagen (chondrocytes produce type I1 collagen) in the

serum of patients during an acute attack of RPC (15)

Alternatively, McAdam et a l have suggest that RPC

may actually fall in the spectrum of a systemic vasculitis

(5)

Pathology Relapsing polychondritis may involve hy-

aline, elastic, o r fibrocartilage (9) One of the most striking

histological features is the loss of the normal basophilic

staining of cartilage as seen in hematoxylin and eosin

(H&E) preparations ( 16) The cartilage, instead, becomes

acidophilic, chondrocytes degenerate, and the matrix frag-

ments The perichondrium is infiltrated with plasma cells,

lymphocytes, and neutrophils, and the normally sharp

interface between the cartilage and perichondrium bc-

comes indistinct and irregular Ultimately, the cartilage is

destroyed and replaced either focally or diffusely with

granulation and scar tissue

Differential Diagnosis Relapsing polychondritis

must be distinguished from Wegener’s granulomatosis sys-

temic vasculitis, rheumatoid arthritis, Reiter’s syndrome,

gout, and infectious perichondritis and external otitis

Involvement of the auricle is distinctly uncommon i n

Wegener’s granulomatosis, whereas mucosal lesions are

rare in RPC ( I ) The absence of renal involvement and

hypertension argue against the diagnosis of systemic vas-

culitis ( l ) According t o McAdam et al., the arthritis of

RPC can be distinguished from rheumatoid arthritis by

the following features: (a) It is generally seronegative, (b)

it is usually nonnodular and rarely leads to deformity, (c)

it tends to be asymmetrical and to spare the forefeet, and

(d) i t has a propensity for the sternoclavicular, sternoma-

nubrial, and costochondral joints ( 5 ) The absence of

urethritis eliminates Reiter’s syndrome A normal serum

uric acid value and failure to demonstrate urate crystals

in joint aspirates are against the consideration of gout

Infectious perichondritis and otitis externa are most often

seen following trauma or burns of the auricle or in elderly

diabetics and immunocompromised patients (8) Failure to

respond to appropriate antibodies is helpful in eliminating

these possibilities

Treatment and Prognosis Corticosteroids are gen-

erally effective in abating the acute manifestations of the

disease In severe cases immunosuppressive drugs such

as azathioprine may have to be used, whereas in milder

ones, nonsteroidal, anti-inflammatory drugs have had peri- odic success

The clinical course of RPC is variable In most in- stances it tends to be low-grade and smoldering over a

course of many years whereas in others it may be quite fulminant A benign course early in the disease, however does not preclude aggressive behavior later (7) In a review of 132 cases, Arkin and Masi noted that 29 patients (22%) had died of their disease after a mean interval of 5.25 years (4) Almost half of the deaths were due to respiratory tract involvement

1I.D Focal Osteoporotic Bone Marrow Defect

Etiology and Pathogenesis The focal osteoporotic

bone marrow defect (FOBMD) represents a localized accumulation of either fatty or red marrow within the jaws Although the etiology and pathogenesis of this lesion are unknown, three possibilities have been formulated: ( a )

persistence of embryonic marrow remnants (l-S), which are known to occur normally in various areas of the jaws, particularly the maxillary and mandibular premolar-molar regions, angle of the mandible condylar processes, and maxillary tuberosities (1.6): (b) altered regeneration of bony trabeculae in an area of previous trauma, local in- flammation, or tooth extraction ( 1,4,7-9); and (c) bone re- sorption secondary to marrow hyperplasia in response t o an increased demand for blood cells ( I ,3.5,7,9, IO) The evi- dence and discussions in support of and in opposition to these hypotheses can be found in several reports (4.5,7- IO)

Clinical Features and Radiography This lesion is

rare Standish and Shafer found only 18 examples (0.2%) among 8700 oral biopsies (4) Barker and his associates

in a review of 47,000 oral surgical specimens, were able

to identify only 197 cases (0.4%) (7) Makek and Lello

detected just 20 FOBMD over an 1 I-year period (8) A similar number was discovered by Schneider et al over a

12-year time span (9)

The mandibular molar region is affected in 70-8996 of the cases (4,5,7-9) In the maxilla, the tuberosities are the most favored locations (4,5,7,9); involvement of the anterior segment is highly unusual (9,l l ) Over 65% occur

in women (43.7-9, 12) and whites are primarily affected (approximately 94%) (4.5.7) The age for a l l patients

ranges from 7 to 79 years (average, 42.6 years; 4,5,7-9) and more than 50% of the cases are found in individuals

in the fourth, fifth, and sixth decades of life (7-9) Although several investigators have reported an associ- ation between the FOBMD and sickle cell anemia

Figure 22 Focal osteoporotic bone marrow

defect: The lesion appears as a moderately

defined radiolucency traversed by both fine

and coarse trabeculations

(9,10.13), an analysis of 36 patients with generalized bone

marrow hyperplasia occurring in conjunction with various

types of chronic anemias failed to reveal any concomitant

examples of FOBMD (7)

pain or swelling (8,11,12,14) However, most are asymp-

tomatic and are found incidentally on radiographs in which

they appear as a nonspecific, poorly, moderately, or well-

defined radiolucency that is sometimes traversed by fine or

coarse trabeculations (Fig 22) It may vary from only a few

millimeters to several centimeters, but most measure 1 cm

or less in diameter (4,5,7-9) Although typically unilateral,

some have demonstrated a bilateral distribution (5,8,10)

The lesion may appear independently or within, or in close proximity to, a variety of other conditions, such as an im- pacted tooth (usually a mandibular third molar), periapical cementa1 dysplasia, gigantiform cementoma, osteomyeli- tis, enostosis, exostosis, fibrous dysplasia, retained root tip previous fracture or extraction site, periapical granuloma,

or ameloblastoma (5,7,8,11)

Pathology The FOBMD consists of red marrow composed of normocellular erythroid and myeloid ele- ments, with occasional megakaryocytes, fatty marrow, or

a combination of both (4,5,7,8,11,14; Fig 23) Lamellae

of bone, which are usually present, are long, narrow, and devoid of a peripheral rim of osteoblasts (4,7)

Figure 23 Focal osteoporotic bone

marrow defect: Fatty marrow as well as

red marrow composed of erythroid and

myeloid elements with occasional meg-

akaryocytes are evident (H&E, X40)

Diseases of the Bones and Joints l081

Treatment and Prognosis Because of the lack of

roentgenographic specificity, the lesion should be explored

surgically (5) However, once the diagnosis has been

established, no treatment is necessary (15)

Differential Diagnosis The FOBMD may be con-

fused radiographically with the traumatic bone cyst How-

ever, this latter lesion is more common in men, is more

likely to be found in individuals younger than the age of

30, and on surgical exploration, presents as a cavity devoid

of contents or containing only a small amount of straw-

colored fluid (see Chap 21 of this text for a more complete

discussion)

1I.E Cortical Defects of the Mandible

Terminology In 1942, Stafne first described a dis-

tinctive osseous anomaly of the posterior lingual aspect

of the mandible in 35 patients Follow-up of some of

these individuals for as long as 1 I years failed to disclose

any change in size of this lesion, thus resulting in the

coinage of the term static bone cyst (1) Subsequently,

numerous cases have been reported using this same desig-

nation or under the terminology of latent bone cyst, Stafne

cyst or defect, mandibular embryonic defect, aberrant

salivary gland defect, ectopic glands of the mandible,

aberrant salivary gland tissue in mandible, lingual mandib-

ular bone cavity, lingual mandibular bone concavity,

idiopathic bone cavity, lingual cortical defect of the

mandible, congenital defect or depression of the mandible

containing salivary gland tissue, salivary gland inclus-

ion in the mandible, static bone cavity, developmental

salivary gland defect of the mandible, and developmental

lingual mandibular salivary gland depression Richard and

Ziskin, in 1957, identified a similar entity in the anterior

lingual aspect of the mandible (2) Subsequent anthropo-

logical studies demonstrated additional defects in the ante-

well

1I.E I Posterior Lingual Cortical Defect

Clinical Features The posterior lingual cortical de-

fect (PLCD) represents a solitary, asymptomatic, some- times palpable, nonprogressive cortical depression, most often located between the angle of the mandible and first molar, below the mylohyoid line, and inferior to the mandibular canal (1,6-9) This variant has been found in from 0.1 to 0.48% of radiographs (7,10,1 I), and in from 0.7 to 1.8% of dry mandibles (7,12-14) With only a few exceptions, all patients have been men (1,7,10,1 I , 14,15- 19) and the highest incidence has been in the fifth, sixth, and seventh decades of life (1,7,14,17,19)

A much smaller number of PLCD have been identified

in the ascending ramus, either along the posterior border inferior to the condylar neck (20,21), or in the mandibular sulcus superior to the mandibular foramen (22) These

were asymptomatic, preponderantly affected men, and occurred in the third through the fifth decades

Radiography The PLCD typically appears as a well-

circumscribed, unilocular, round or oval radiolucency, usually with a dense, sclerotic border (1,7,9-12,14,17- 19,23,24; Fig 24) Less frequently, it may appear as multiple radiolucencies (24,25); a bilocular radiolucency (17,26); a unilocular lesion, simulating a dentigerous cyst

(8); or a radiolucency composed of two distinct locules

(27)

The size may vary from only a few millimeters to several centimeters (1,17), with the widest diameter of ovoid lesions being parallel to the inferior border of the mandible (1) The latter may exhibit an interruption in its continuity (1,10,17), and the mandibular canal may be displaced superiorly (1,7,11,12,17,18,23,24) when a large

radiolucency (large arrow) is situated below the Inferior alveolar canal (small

Posterior lingual cortical defect of the mandible: A unilocular, oval

, : arrow) In the molar region A sclerotic border is not evident In this example

I (Courtesy of WG Fischer, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA.)

defect is present However, the PLCD is not associated

with any clinically apparent deformity unless it involves

the lower border of the mandible, in which case a

“notching” may be palpated ( l )

The most important factor in establishing the diagnosis

is the ability to demonstrate that the concavity is open on

the lingual surface with an intact corticated base This is

best demonstrated by axial computed tomography (19)

This modality has also delineated three types of PLCD ac-

cording to their relation to the buccal cortical plate: (a) bot-

tom of the concavity does not reach the buccal cortical

plate; (h) bottom of the concavity does reach the buccal

cortical plate but does not produce expansion or distortion

of the plate; and (c) bottom of the concavity reaches the

buccal plate and causes expansion ( 19) Submandibular si-

alography has also been used to investigate these lesions

(28-32)

In a study of dry mandibles, defects less than 2 mm in

depth were difficult to visualize on roentgenograms This

particular finding led to the speculation that the incidence

of the PLCD might be higher than generally perceived

(12) This might also be why it is often not observed

in individuals before middle age, because the necessary

amount of bone resorption has not taken place for it to

become manifest radiographically (12)

The lesions occurring along the posterior border of the

ascending ramus also appear as round or oval radiolucen-

cies (20,21) The largest dimension is parallel to the long

axis ofthe ramus (20)

Pathology On gross inspection the PLCD appears

a s singular or multilobular concavities, pits, or depressions

(14) They are usually unilateral (4) and are round or oval,

with well-defined borders and a roughened cortical plate

( 1 2) The floors of the depressions vary from smooth to cor-

rugated (14) Most contain salivary gland tissue (9,19,33-

37) Others contain fat, connective tissue, muscle, or

lymphoid tissue (9,12,19.24,38), although some are devoid

of contents (23,24,38,39) The defects detected in the man-

dibular sulcus are concave with smooth margins and mini-

mal or no reactive bone at their margins (22)

Etiology and Pathogenesis Some investigators have

proposed that the PLCD forms as a congenital defect

owing to entrapment of the upper portion of the submandi-

bular gland during the development of the mandible

(1,28,29,37,40) in conjunction with an infolding of the

lower border of the mandibular cortical surface (32)

However, the absence of lingual defects in embryos and

children younger than 1 I years (40) argues effectively

against this concept ( l4,4 I ) It is more likely that the

PLCD represents an area of resorption of the mandible in

response to pressure from a hyperplastic submandibular

gland (7,10.12,17.24,37,40,42,43) Because the process of

resorption is slow and progressive, it becomes detectable radiographically only by middle age (9) The absence of salivary gland tissue in some of the defects produced by this mechanism may be due to the displacement of the gland at the time of surgery (24,33) or to the eventual disappearance of glandular tissue as a result of pressure from its entrapped secretions (32) Conversely, the pres- ence of connective tissue, fat, muscle, or lymphoid tissue

in other defects may be explained on the basis of the biopsy having been inadvertently taken from surrounding structures in the submandibular space (12,24) Lello and Makek have suggested that the PLCD develops as a result

of a relative ischemia of the lingual cortex in an area adjacent to the passage of the facial artery (39)

The examples of PLCD found along the posterior border of the ascending ramus are presumed to develop

as a result of entrapment of portions of the parotid gland (2 l ) Those noted in the mandibular sulcus may arise from erosion of the cortical plate caused by an aneurysm

of the inferior alveolar artery or a benign soft-tissue neoplasm of neural sheath or vascular origin; that is,

a neuroma, neurilemoma, or hemangioma (22) These proposed origins have an important clinical significance

If a vascular neoplasm or aneurysm there is the possibility

of an increased risk of injecting anesthetic solution di- rectly into a vessel A neural sheath origin increases the likelihood of requiring more solution to achieve adequate anesthesia (22)

Treatment and Prognosis Because these lesions are

asymptomatic and nonprogressive and present such a characteristic radiographic appearance, any therapeutic form of intervention is unnecessary (10,36); however, continued radiographic follow-up is recommended (7,9,

2 1.36) Surgical exploration and biopsy are indicated only

in those patients who are radiographically atypical or to

rule out the possibility of other lesions (7,9)

Differential Diagnosis The entity with which the

PLCD is most commonly confused is the traumatic bone cyst However, the latter, in contrast with the former, almost invariably lies above the mandibular canal (44) Additionally, the traumatic bone cyst occurs in proximity

to the apices of roots of teeth and is frequently accompa- nied by a change in size as well a s possible cortical expansion ( I O ) The focal osteoporotic bone marrow de- fect may also present a radiographic appearance similar

t o that of the PLCD Other conditions that should be considered in a differential diagnosis when seen in lateral

or panoramic views include the aneurysmal bone cyst, early stage cementifying or ossifying fibroma, ameloblas- toma, central giant cell granuloma, or a primary or meta- static malignancy These can often be ruled out when findings on cross-sectional tomography include an absence

Diseases of the Bones and Joints 1083

of a lingual cortical plate and the presence of a mandibular

depression (26)

II.E.2 Anterior Lingud Cortical Defect or

Depression

Etiology and Clinical Features This variant of cor-

tical defect was first reported in 1957 by Richard and

Ziskin (2) They are found anterior to the first molar and

reflect resorption of the lingual cortical plate in response

to pressure from the sublingual gland (9,41) Most are

asymptomatic and are found incidentally during a radio-

graphic examination Most such lesions are located i n

the canine or premolar areas; the incisor region is only

infrequently involved Men are affected five times as often

as women The mean age of patients is 44.5 years, with

60% being in the fifth and sixth decades (9)

Despite apparent similarities in their etiology and

pathogenesis, certain differences exist between the poste-

rior and anterior lingual defects First, in the case of

the anterior lingual cortical defect, (ALCD), a distinct

concavity can frequently be palpated (42,45), and its

location can be detected from a contrast in translucency

to indirect light reflected from a mouth mirror (42)

Second, an evaluation of dried specimens has disclosed

that ALCDs, in contrast with PLCDs, are smooth depres-

sions that show no evidence of definite borders or destruc-

tion of the cortical bone (12)

Radiography The ALCD may be unilateral, but it is

more often bilateral (12), and only one example has

been described as multilocular (46) It has been variously

described as a discrete ovoid radiolucency ( 4 9 , triangular-

shaped radiolucent lesion (47), a well-circumscribed round

radiolucency (41), a cyst-like lesion (48), or a gourd-

shaped radiolucency (49) Usually, it is well-circum-

scribed and only occasionally exhibits dense sclerotic

borders (9) Most are located either entirely subjacent to

the root apices or are partially superimposed over the

apices, thus mimicking a periapical lesion, such as a cyst

or granuloma I n some instances, it appears between the

roots of adjacent teeth or i n an edentulous area The size

ranges from 0.5 to 2.0 cm with a median of 1.2 cm (9)

Pathology Most ALCDs contain salivary gland tis-

sue (9,50), and surgical exploration has disclosed a conti-

nuity with the sublingual gland in these cases (9) Fat or

connective tissue have been found in others, and some

have been found to be empty (9,42,50) This last observa-

tion may be due to a disturbance of the normal relation

of the defect to adjacent tissue (41)

Treatment and Prognosis Unlike the PLCD, the

anterior lesion can be diagnosed definitively only by surg-

ical exploration and histological examination (9,473 l )

However, once the diagnosis has been established, no further treatment is indicated (50)

Differential Diagnosis Because the ALCD often oc-

curs between or below the roots of teeth (9,42,45,50,52),

it must be differentiated from early-stage periapical ce- mental dysplasia, periapical granuloma or cyst, residual cyst, odontogenic keratocyst, lateral periodontal cyst, or traumatic bone cyst Unless simultaneously involved with extensive caries or with advanced periodontal disease, resulting in pulpal necrosis, the teeth adjacent to ALCD respond normally to vitality tests This finding can be used to rule out the inflammatory odontogenic cysts An occlusal projection that shows the lingual surface of the mandible is useful in distinguishing the defect from other cysts or a benign tumor (50)

II.E.3 Anterior Buccal Cortical Dcfict

The features of the anterior buccal cortical defect (ABCD) were first delineated by Arensburg et al in 1989 (3) and subsequently by Kaffe et al in 1990 (4) It is indicative

of a specific remodeling pattern of the mandible, has been found in 37% of 970 dry mandibles, and exhibits a significantly higher prevalence in children The ABCD is always bilateral, extending on each side of the symphysis from the mental protuberance to the area of the mental foramen and between the basal and alveolar parts of the mandibular body, usually below the level of the mental foramen It measures 10-15 mm long, 3-6 mm wide, and 1.5-4.0 mm deep, with its long axis running parallel to the inferior border of the mandible The depth is greater

in children, but becomes shallower and tinally almost disappears with age

The ABCD is asymptomatic and exhibits varying de- grees of radiopacity or radiolucency, depending on its depth The borders may be well-demarcated or poorly defined In general, its radiographic appearance is quite similar to that of the ALCD Consequently, distinction between these two entities is made on the basis of inte- grated information (Table 5 )

It is important to recognize this defect for what it

is, because once the diagnosis has been established, no treatment is necessary Radiographic follow-up, however,

is appropriate Surgical intervention should be considered only in cases of abnormal growth or suspected malig- nancy

II.E.4 Posterior Buccal Cortical Defect

This variant, found in dry mandibles by Kocsis et al in

1992 ( 3 , is located posterior or lateral to the molars and superior to the mylohyoid line, with its long axis oriented

Table 5 Differentiation Between the Anterior Lingual

Cortical Defecl (ALCD) and the Anterior Buccal Cortical

Defect (ABCD)

More clearly defined margins Less clearly defined margins

Mostly i n adults Predominately in children

Most often bilateral hut m a y Always hilakml

appear with age

also he unilateral

So/rr<.c,: Ref 4: Sec I1.E

anteroposteriorly It was observed i n only 4 of 8282

(0.05%) specimens, all of which were from men The

average age of the subjects was estimated to have been

42.5 years, and the mean measurement was 13 X 6 X 5

mm Radiographically, one case was superimposed on the

roots of a tooth and appeared as a periapical lesion

The etiology of the PBCD is uncertain Because there

was no evidence of inflammation or trauma i n the speci-

mens examined Kocsis et al have postulated that it may

result from erosion caused by an aneurysm, lymphoid

nodule, or neural neoplasm, or that it may merely rcpre-

sent an anatomical variant of the normal architectural

topography of the mandible (S)

1I.E Paget’s Disease of Bone

Clinical Features Paget’s disease of bone (osteitis

deformans) is a disorder of uncertain etiology, character-

ized by increased osteoclastic and osteoblastic activity,

resulting i n the disorderly production of abnormal highly

characteristic bone It appears to occur only in humans

( l ) In I877 James Paget published the first detailed

clinical and pathological description of the disease (2)

His patients had extensive, deforming disease that he

believed had an infectious etiology Hence, his reason for

naming the disorder osteitis deformans Earlier case re-

ports were published by Wrang and Wilks in 1867 and

1869 respectively ( 2 4 )

Although the patients initially described by Paget had

extensive widespread disease i t was later recognized that,

i n up to 7 0 4 or more of cases, the disorder is limited to

one or a few small foci that may be asymptomatic (S)

This has made estimation of the true incidence somewhat

difficult although most estimates range bctwccn 3 and

5%; of the adult population older than the age o f 40 years

(6-1 1 ) This figure rises to I 1 % for persons older than 80

years o f age (9,12,13) The disease is diagnosed in most

patients between the ages of SS and 70 years The disease

is so rare in younger individuals that the diagnosis should

be seriously questioned i n anyone younger than the age

of 40 years (13-18) Those cases reported i n children probably represent congenital hyperphosphatasia, rather than Paget’s disease (14) Men predominate with ratios ranging from 4:3 to as high as 3: I (S$, I I , 19)

There appears to be a definite variation i n geographic and racial distribution The disorder is much more com- mon i n the United Kingdom than i n the United States It is particularly uncommon in Scandinavia Africa, the Middle East India, Japan and China (X, 13 I8,20,2 l ) Emigrants from areas having a high incidence retain their relative risk for the disease (19.22)

A positive family history can be elicited in up to 14% of patients, and the risk of a first-degree relative developing the condition increases to approximately 20%

if the patient was diagnosed at an early age or had deforming disease (S.23,24)

Although the disease is polyostotic in 90% of cases, patients can take comfort i n the fact that i t is uncommon for additional new sites t o develop later i n bones that were normal at the time of initial diagnosis (7) Disease

at affected sites may remain limited or may progress ( 13) Progression of the disease is usunlly slow One series measured the progression to be I8 mm/year but frequently

it is much slower (25) The bones involved i n descending order of frequency, are the lumbar vertebrae the sacrum, the skull, the pelvis, the femur, the tibia, the clavicle, the humerus, and the ribs For unknown reasons the tibula and the bones o f the hands and feet are seldom affected

( 14.20,26)

Involvement may be asymptomatic I n symptonlatic patients the clinical presentation varies with the distribu- tion of the disease The most frequent complaints of symptomatic patients include bone pain, skeletal deformi- ties secondary degenerative joint disease, and increascd warmth of overlying skin (Q3.27) The incidence o f congestive heart failure is said to be increased i n pagetic patients Although this has been attributed to the presence

of arteriovenous shunts this has never been proved and

in many instances the congestive failure may simply be

;I manifestation of prinmry cardiovascular disease i n these older patients Neurological complications are common and result from pressure exerted by the pagetic bone on cranial nerves, the spinal cord and nerve roots, or from changes i n the weight-bearing ability of the bone (21 ) These complications include niuscle weakness, paralysis, deafness, and rectal and urinary incontinence ( 13) The skull is the third most common site of involvement (26) The cranial bones are more frequently affected than the facial bones, and the maxilla is much more comtnonly

Diseases of the Bones and Joints 1085

involved than the mandible (XJ28.29) Involvement of

the skull is associated with a variety of signs and symp-

toms, the most familiar being a progressive increase in

hat size Fortunately, compression of the cerebral hcmi-

spheres is rare because most of the pagetic bone is dcpos-

ited i n the outer table (20,30) Accumulation of this

abnormal bone may, however, compromise the neural

foramina, including the foramen magnum (30) Hearing

loss occurs in 30-50% of patients with temporal bone

involvement Causes for the dcafncss arc multifactorial

and include involvement of the ossicles, auditory nerve,

cochlear compression, and possibly changes in the acous-

tic properties of the bone owing to changes i n bone

density (S, 1 1 )

Cranial nerves other than VI11 are rarely compromised

I n rare instances, optic atrophy develops secondary to

compression of the optic nerve in its foramen (30) Depo-

sition of’ new bone i n the orbit, the superior orbital fissure

and the optic canal can result in proptosis, extraocular

muscle palsies and optic atrophy In other instances, the

presence of retinal hemorrhages and pigmentary changes

rellect vascular changes, and it may be difficult, if not

impossible t o decide whether these are complications of

Paget’s disease or primary cardiovascular disease (20)

Distortion o f the bones of the base of the skull

(platybasia), scen in about one-third of patients with skull

involvement may occasionally result i n neurological ab-

normalities Increased pressure on the pons or cerebellum

may be responsible for progressive muscle weakness and a

decrease in coordination and control of respiration ( I2,I3)

Patients with jaw involvement may complain o f pain

Excessive deposition of pagetic bone in the maxilla pro-

duces ;I lion-like faces (leontiasis osseum), whereas simi-

lar deposition i n the mandible results in mandibular prog-

nathism (19) Increase in the size of the dental arch causes

teeth to become spaced Teeth may become loosened

owing t o bone resorption or come loose because of hyper-

cementosis (19) If dentures are worn, the patients may

complain of improper fit (29)

Neoplastic complications of Paget’s disease include the

development of sarcomas and giant cell tumors Sarco-

matous change occurs in approxilnately 1 %; of a l l patients

with Paget’s disease (31-33) I t is more common in

widespread disease, for which the incidence is between 5

and 1 0 % (13,3 1.32) In a l l instances the sarcomas arisc

only in the pagetic bone The classic patient is older than

SO years of age and has polyostotic disease that has been

present for 10-15 years Thc location of the tumors is

similar to the sites of involvement in uncomplicated Pag-

et’s disease, with two exceptions: These are the frequency

of humeral involvement (second most common site) and

the infrequent involvement of the vertebrae ( 2 6 3 1 ,33)

The most common clinical complaint is constant localized pain of recent or increased severity at the site of the neoplasm This may be associated with a palpable mass ( I8.26,33) Radiographically the tumors may be lytic sclerotic, or mixed but arc most frequently lytic (33) A

rapidly arising alkaline phosphatase may signal the onset

of sarcomatous change; however, markedly elevated levels are also seen in uncomplicated polyostotic Paget’s disease (26) The sarcomas have gross and microscopic features similar to those arising in patients without Paget’s disease The vast majority are osteosarcomas, followed by fibro- sarcomas or chondrosarcomas (3 133.34) Although non- malignant bone in the area shows the features of Paget’s

disease, this is not true of the neoplastic bone (31) These

tumors typically have a poor prognosis that appears to be independent of the type of sarcoma and the histopathologi- cal grade (33) The S-year survival is approximately 8% The cause of the poor prognosis may be multifactorial, including the propensity for the axial skeleton, which makes surgical removal more difficult, and the delay in diagnosis because of signs and symptoms similar to the underlying Paget’s disease (33)

Giant cell tumors in patients without Paget’s disease typically affect the metaphyses and epiphyses of long bones and are rarely found in the skull Most patients are between 20 and 40 years of age Conversely, giant cell tumors arising i n pagetic individuals characteristically involve the skull (calvarium and facial bones) and occur

in individuals older than 40 years of age (3.5-37) Their occurrence complicating Paget’s disease is uncommon They typically form progressively enlarging painless masses and may lead to nasal obstruction and epistaxis The differential diagnosis includes central giant cell tu- mor, brown tumor of hyperparathyroidisrll, aneurysmal bone cyst, chondrosarcoma, and osteosarcoma, with prom- inent giant cell components (3,6) The giant cell tumors complicating Paget’s disease tend not to be as aggressive

as those occurring in patients without Paget’s disease and can usually be treated i n a conservative manner

There have been reports of multiple myeloma cocxist- ing with Paget’s disease The incidence of the two diseases occurring i n the same patient is estimated at 1 :SOO,O00 and most believe this to be nothing more than a fortuitous association ( 3 x 4 0 )

Serum calcium and phosphorus values are typically normal because the increased osteoclastic activity is bal- anced by increased osteoblastic activity with reutilization

of calcium and phosphate ions (15,lX) Increased serum alkaline phosphatase activity reflects the increased osteo- blastic activity (18) Elevated urinary levcls of hydroxy- proline result from the increase in osteoclastic activity ( 13, I S 19) Measurement o f bone-specific acid phospha-

Figure 25 Sclerotic areas of pagetic

bone producing a “cotton wool” appear-

ance (Courtesy of HD Curtin Eye and

Ear Hospital, Pittsburgh, PA.)

tase is useful in evaluating for localized disease that

may be associated with an elevated bone-specific alkaline

phosphatase, but a normal total serum alkaline phospha-

tase Bone-specific alkaline phosphatase is also helpful in

patients with hepatic disease, which may contribute to an

elevation of the total serum alkaline phosphatase (12)

Similarly, urinary levels of pyridinoline are more accurate

in detecting increased osteoclastic activity in limited dis-

ease than measurements of urinary hydroxyproline (1 2)

Radiography Radiographic changes can be conve-

niently divided into three phases: an initial osteolytic

phase (most common in the skull and tubular bones), a

combined osteolytic and osteoblastic phase, and a subse-

quent osteoblastic (inactive) phase (most common in the

axial skeleton; 1,12,13,20,25) All phases may be present

simultaneously in the same or in different bones (25) The

osteolytic phase is characterized by the production of

osteolytic areas, with disappearance of the normal osseous

pattern This is frequently seen in the frontal bone of the

skull, where it is termed osteoporosis circumscripta In

the long bones it produces a V- or wedge-shaped radiolu-

cent area described as having the shape of a “blade of

grass” or a “flame” (13) Early jaw involvement is best

appreciated around the teeth The lamina dura disappears

and resorption of bone at the apices of teeth may be

mistaken for granulomas Vitality testing, however, will

demonstrate that these teeth remain viable The combined

phase is characterized by a widened cortex with loss of the

normal contrast between cortex and medulla Trabeculae appear as coarse striations, often widely separated Thick- ening of the cortex of the vertebral bodies gives them a

“picture frame” appearance, whereas areas of increased bone density in the skull imparts a “cotton wool” appear- ance (20; Fig 25) Enlargement of the cranial vault gives

it the appearance of overriding the facial bones This along with involution of the base of the skull, gives a

radiographic appearance referred to as the tam-o-shanter skull (1,20; Fig 26) Involvement of the jaws is less frequent than involvement of the cranial vault A similar cotton wool pattern is seen (Fig 27) This may result in antral occlusion (19) Hyperplasia of the cementum, greater than that seen in any other condition, is also

characteristic Radiographic changes in the jaws tend to

be more generalized than in the long bones (19) In the osteoblastic (sclerotic) phase, evidence of osteolysis is absent, and roentgenographically the appearance is en- tirely that of osteosclerosis (13)

Increase in the diameter of bones, as seen in radio-

graphs, is characteristic of Paget’s disease and serves to distinguish it from other conditions, such as metastatic car- cinoma (10,12) Two types of fractures are seen: cortical stress fractures and true fractures Stress fractures occur along the convex aspect of the cortex of the deformed long bones They lie perpendicular to the surface of the cortex They are usually asymptomatic These stress fractures bear

no relation to external trauma Complete fractures may oc-

Diseases of the Bones and Joints 1087

cur following significant or minor trauma They occur in

the long tubular bones, where they are characteristically

transverse and perpendicular to the external cortex, or in

the vertebrae These fractures may be slow to heal, and the

callus may be involved in the pagetic process (13,20)

Scintigrams are more sensitive in detecting small foci

of active disease Approximately 10% of patients in whom

plain radiographs are normal will show evidence of pag-

Figure 26 Tam-o-shanter skull: Enlargement of the cranial

vault and platybasia have produced the appearance of ovemding

of the facial bones (Courtesy of N Abrahamsen University of Pittsburgh School of Medicine, Pittsburgh, PA.)

etic activity on scanning (5,ll) Little or no uptake may

be seen in the inactive phase; however, the changes in the plain radiographs are characteristic in this phase (25)

Pathology The gross appearance of pagetic bone varies with the stage of development of the disease In early lesions (osteolytic phase) the bone is osteoporotic In the skull the inner and outer tables and the diploid bone are thinned, rather than thickened, and have a red-purple hue

Figure 27 Paget’s disease with pro-

nounced involvement of the maxilla (Courtesy of J Guggenheimer, Unlver- sity of Pittsburgh School of Dental Medicine, Pittsburgh, PA.)

Figure 28 Pagetic calvarium: The bone 1s markedly thickened

but porous It has the appearance and feel of pumice stone

Figure 29 Paget's disease of bone:

Howship's lacuna containing a multinu-

cleated osteoclast and fibrous tissue

Also note the typical mosaic pattern of

the bone (H&E, X250)