Essentials-of-Oral-Pathology-3rd-Edition by purkait

478 Essentials of Oral Pathology

Proteinosis in Two Siblings: A Report from India. J 42. Van Dis ML, Allen CM, Neville BW. Erythematous
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40. Sonis ST, Fazio RC, Fang L. Principles and practice of adolescent boy with a history of dental problems. J Oral
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Birth Defects 1971;7:153.

PAGET’S DISEASE OF BONE Sites: Paget’s disease has a predilection for the
(OSTEITIS DEFORMANS) weight bearing areas of the body, especially the
vertibral column and femur, etc. The skull, pelvis
DEFINITION and sternum, etc. are also commonly involved.
Among the jawbones, maxilla is affected twice
Paget’s disease is a relatively uncommon bony as often as mandible.
disorder characterized by excessive, uncoordi-
nated phases of bone resorption and subsequent NATURAL HISTORY OF THE DISEASE
deposition of new bone in the same area. The
disease finally results in severe distortion and The natural history of paget’s disease can be
weakening of the affected bone. Paget’s disease divided into three progressive and overlaping
was first reported in the year 1877 by Sir James phases:
Paget. A. Initial predominantly osteolytic phase.
B. An active stage of mixed osteolysis and
ETIOLOGY
osteogenesis.
The disease is a focal alteration in the morpho- C. Predominantly osteoblastic or sclerotic final
logy and histopathology of bone which exhibits
disorganized formation and remodeling of phase.
osseous structures, unrelated to the functional
requirements. PRESENTATION (FIGS 15.1 AND 15.2)

The exact etiology of the diseases is not known, • Most of the patients complain initially of a
although several factors have been implicated, deep and aching bone pain, with bilaterally
which probably trigger the disease, these factors symmetrical swelling of the involved bone
include the following: (Fig. 15.1).
• Genetic abnormality
• Inflammatory reaction to the bone
• Circulatory disturbances
• Defective connective tissue metabolism
• Slow viral infections (especially paramyxo-

virus)
• Autoimmune disorders
• Endocrine abnormality.

CLINICAL FEATURES Fig. 15.1: Paget’s disease of bone causing
swelling of the maxilla
Incidence: The incidence rate is about 2.5 percent
of all persons over 40 years of age.

Age: The disease can occur at any age but usually
most of the patients are in their fifth, sixth and
seventh decade of life.

Sex: Males are slightly more commonly affected
than females (3:2).

480 Essentials of Oral Pathology

Fig. 15.2: Intraoral view of the same patient showing stance’. Moreover, these patients often have
expansion of the maxillary bone a characteristic waddling gait.
• In Paget’s disease, involvement of the facial
• The pain can be sometimes so severe that the bone is referred to as “leontiasis ossea” and
patient is unable to move the affected organ. patients often have a grotesque appearance
Many cases however are asymptomatic and of the face due to severe bony deformity.
the bony abnormality is detected only during • The patients may develop headache, deaf-
routine radiographic examinations. ness, blindness and facial paralysis, etc.
which occur due to the narrowing of the
• More deformity in the bone is usually obser- skull foramina and subsequent compression
ved in the stress bearing areas, e.g. spine, of the cranial nerves passing through them
femur, sacrum and pelvis, etc. (both sensory and motor disturbances are
seen).
• The disease in the weight bearing areas of the • Progressive enlargement of the skull, bowing
body may cause severe bowing deformity and of the legs with thickening and curvature of
thereby results in a typical ‘monkey-like the spine are commonly seen.
• Increased localized temperature of the skin in
the affected areas of bone is often noticed.
• Due to the gradual enlargement of the skull,
patients often feel difficulty in wearing their
old hats.

RADIOLOGICAL FEATURES

The radiographic findings of Paget’s disease of
bone are highly variable depending upon the
stage of the disease.

Oral manifestations of Paget’s disease

• Denture-wearing people often complain of tightness of their old dentures with poor fit due to progressive
enlargement of the jawbones, especially the alveolar ridge.

• Facial paralysis due to compression of the nerve as a result of obliteration of the cranial foramina.
• Maxillary bone is affected by the disease more often than the mandibular bone.
• Diastema, loosening of teeth and difficulty in lip closure is common and all the teeth in the jaw are vital.
• Movements and migration of teeth with concomitant development of malocclusion is a common problem

in dentulous patients.
• Flattening of palate, retroclination of incisors and palatoversion of posterior teeth often occurs.
• Moreover, the disease may cause necrosis of the gingiva and the underlying alveolar bone; due to excessive

internal pressure in the jaw.
• Gross hypercementosis of teeth is a characteristic finding of Paget’s disease and the teeth are often

fused with the jaw bone.
• Extraction can be difficult in these patients because of fusion of tooth with the jaws, post-extraction

hemorrhage and chances of development of osteomyelitis, etc.
• Maxillary lesions often cross the midline and involve both quadrants of the jaw.
• Pathological fractures in the affected bones may occur, since these bones are very weak despite their

gross thickening.
• Osteogenic sarcoma develops in about 10 percent cases of pre-existing Paget’s disease of bone.
• Besides osteosarcoma, giant cell tumors can also develop from the pre-existing Paget’s disease of

bone.

Diseases of Bone 481

• In the initial stage of the disease, random
osteoclastic bone resorption occurs, and the
bone is replaced by a highly vascularized
cellular connective tissue.

• The osteoclasts are usually larger and may
even contain over one hundred nuclei.

Fig. 15.3: Radiograph shows cotton-wool appearance of Fig. 15.4: Photomicrograph of Paget’s disease of bone
maxillary bone in Paget’s disease

• Initially, there is presence of only radiolucent Key points of Paget’s disease
areas in the affected bone due to decreased
density. • Paget’s disease is a bony disorder characterized
by repeated resorption and deposition with
• In the next stage, radiographs of the involved severe weakening and deformity of the affected
bone reveal haphazard arrangement of newly bone.
formed bony trabaculae within the radiolucent
area, which often produces a patchy • The disease mostly affects older individuals, who
radiopaque pattern called “cotton-wool” complains of deep and aching pain, with swelling
appearance (Fig. 15.3). of the involved bone.

• The lesions become more and more radio- • Progressive enlargement of skull causes difficulty
paque due to increased osteosclerosis with loss in wearing old hats and enlargement of alveolar
of normal trabaculations in the later phases ridge makes it difficult to wear dentures.
of the disease.
• Patients may have headache, deafness, blindness
• Lateral skull projection reveals a large, and facial paralysis, etc. due to the narrowing of
prognathic, pagetoid mandible. The maxillary the skull foramina.
lesions often extend to the sinuses and cause
decreased airspace or obliteration. • Flattening of palate, retroclination of incisors and
palatoversion of posterior teeth, diestema and
• Hypercementosis of the tooth, which involves malocclusion often occurs.
the entire dentition.
• Radiograph reveals a typical “cotton-wool”
• Loss of lamina dura and ankylosis with appearance in the bone and hypercementosis of
obliteration of the periodontal ligament space. the teeth.

• Root resorptions are also commonly observed. • Histologically, the bone exhibits rapid resorption
• Monostotic form (involving only a single and subsequent bone deposition with the
presence of multiple reversal and resting lines.
bone) of Paget’s disease of mandible presents
a typical “black beard” image on bone scan. • Laboratory investigation shows markedly raised
serum alkaline phosphatase level.
HISTOPATHOLOGY (FIG. 15.4)
• Paget’s disease increases the tendency for patho-
• Rapid, irregular and exaggerated bone logical fracture of the affected bone as well as
resorption and subsequent bone deposition increases the risk of development of osteo-
are the hallmark features of Paget’s disease. sarcoma.

482 Essentials of Oral Pathology

• In the later stage, deposition of new lamellar • Osteosarcoma
or oven bone within the connective tissue • Metastatic carcinoma
by the osteoblast cells occur and the fatty, • Sclerosing osteomyelitis.
hemopoetic bone marrow is replaced by a
fibrous stroma (fibrosis of bone marrow). TREATMENT

• The newly formed bone may again be Only symptomatic treatments can be done (e.g.
resorbed by the osteoclast cells and thus administration of analgesics to relieve pain).
causing loss of normal architecture of the
bone. Recent investigators believe that adminis-
tration of “calcitonin” may suppress the bone
• This bone resorption and bone deposition resorption and deposition rates in this disease.
alternate rapidly and these changes in the
bony activity are often marked by Surgery may be required in cases of severe
prominent basophilic “reversal and resting bony deformities and in cases of pathological
lines” (these lines indicate the junction fractures of the affected bone.
between alternating areas of bone
resorptions and bone formations). Unfortunately few cases of Paget’s disease of
bone may transform into osteosarcoma.
• The irregular pattern of such lines often
characteristically produces a “jigsaw- FIBROUS DYSPLASIA OF BONE
puzzle” or “mosaic pattern” in the bone.
DEFINITION
• The affected bone becomes thick, sclerosed
and the medullary cavity becomes Fibrous dysplasia is an idiopathic condition, in
which an area of normal bone is gradually
obliterated. replaced by abnormal fibrous connective tissue,
• Chronic inflammatory cells and many which then again undergoes osseous metaplasia
and eventually the normal bone is transformed
dilated blood capillaries are present within into a abnormal dense lamellar bone.
the bone.

LABORATORY FINDINGS TYPES

• During the osteoblastic phase of the disease, Fibrous dysplasia is broadly divided into two
the serum alkaline phosphatase level may be types.
markedly elevated up to 250 Bondansky units
(normal 1.5–5 units). Monostotic fibrous dysplasia: When a single
bone is involved by the disease in a localized area.
• There may be an increased urinary calcium This type accounts for about 80 to 85 percent of
hydroxyproline level during the osteolytic all cases. Jaw bones are frequently affected in this
phase of the disease. type.

• Bone scan may be helpful in determining the Polyostotic fibrous dysplasia: When multiple
exact extent of the disease. number of bones (more than two) are involved
by the disease.
• Although considerable amount of loss of bone
minerals occurs due to resorption, the serum The polyostotic fibrous dysplasia of bone has
calcium and phosphorus levels however are two subtypes:
always normal or near normal.
Jaffey’s type: In which several bones of the
DIFFERENTIAL DIAGNOSIS skeleton are affected in association with café-au-
lait skin pigmentations.
• Acromegaly
• Fibrous dysplasia of bone Polyostotic fibrous dysplasia in association
• Florid osseous dysplasia with Albright syndrome: The condition is
• Hyperparathyroidism characterized by fibrous dysplasia of multiple
• Osteopetrosis bones, café-au-lait skin pigmentation and endo-
• Cementifying or ossifying fibromas crine disturbances.

ETIOLOGY Diseases of Bone 483

The exact etiology of the disease is not known, Fig. 15.5: Fibrous dysplasia of bone
however it is believed to be a non-neoplastic involving the right side of mandible
self-limiting condition caused by some genetic
abnormality. Some investigators believe that Fig. 15.6: Fibrous dysplasia-I
fibrous dysplasia could be a developmental
disorder. Fig. 15.7: Fibrous dysplasia-II

Previously it was considered by many people
that the disease may be initiated by several
predisposing factors which are as follows:
• Liver damage
• Infections
• Glandular dysfunctions
• Neurofibromatosis
• Lipoid granulomatosis
• Trauma
• Abnormal osteoclastic maturation of bone

forming mesenchyme.
However, the role of any of these factors in
the pathogenesis of fibrous dysplasia of bone has
not been fully substantiated.

CLINICAL FEATURES

Age: Fibrous dysplasia usually occurs in the first
and second decade of life. Abnormal bony
growth continues upto late teens or early
twenties.

Sex: The polyostotic type of the disease occurs 2
to 3 times more commonly among females,
however in monostotic type, males and females
are almost equally affected.

Sites: The polyostotic fibrous dysplasia com-
monly involves the skull, facial bones, clavicles,
pelvic bones and long bones, etc.

The monostotic fibrous dysplasia frequently
involves the jaw bones, Maxilla is usually more
commonly affected than mandible.

The mandibular lesions are often truly mono-
stotic in most cases, whereas the maxillary lesions
are frequently associated with other bones, e. g.
frontal, zygomatic and sphenoid, etc.

CLINICAL PRESENTATION (FIGS 15.5 TO
15.7)

• The monostotic type of fibrous dysplasia is
more common (80-85%) than the polyostotic
type.

484 Essentials of Oral Pathology

• It causes a slow enlarging, painless, smooth, periphery. These are seen in those areas,
rounded, unilateral localized swelling of the which overlie the affected bones , e.g. neck,
jaw (Fig. 15.5). buttock back, trunk, thigh and sacral areas.
However these are rarely seen in the oral
• Gradually increasing facial asymmetry with mucosa.
marked swelling of the cheek may be the first • The café-au-lait pigmentations are also seen
sign of fibrous dysplasia in a child, the disease in Von-Recklinghausen’s disease, where they
eventually causes huge deformity of the have a characteristic ‘smooth border’ rather
orofacial region (Fig. 15.6). than a ‘jagged border’.
• Polyostotic fibrous dysplasia of bone with
• Expansion and gradual distortion of the “café-au-lait” skin pigmentations and
cortical plates, displacement of teeth, distur- multiple endocrinopathies like precocious
bances in tooth eruption (many teeth may puberty in females, pituitary adenoma,
even fail to erupt), etc. are commonly obser- acromegaly, goiter, Cushing syndrome,
ved. hyperparathyroidism and hyperthyroidism,
etc. constitute the syndrome called McCune-
• The teeth may be drifted, rotated or misalig- Albright’s syndrome.
ned in the jaw due to the growing bony mass • The precocious puberty in Albright’s syn-
and in many patients severe malocclusion drome occurs in young women and it consists
often develops. of premature vaginal bleeding in the first few
months of life, breast development and
• The monostotic form of the disease never axillary and pubic hair growth, etc. at the age
transforms into polyostotic form with time. of about 2 to 3 years.
• The bony changes in fibrous dysplasia usually
• Although the process is slow enlarging some occur during the period of active skeletal
lesions may be very aggressive, however, pal- growth and it ceases during adult life (at the
pation in the affected area does not elicit pain. time of skeletal maturation).
• On rare occasions, fibrous dysplasia lesions
• The maxillary lesions may sometime extend may undergo malignant transformation and
into the maxillary air-sinus and occasionally develop fibrosarcomas.
into the orbital floor, the later often results in
exophthalmos, proptosis and nasal obstruc- RADIOLOGICAL FEATURES (FIGS 15.8 TO
tions, etc. Moreover, maxillary lesions may
also exhibit obliteration of the canine fossa. 15.10)

• Mandibular lesions mostly concentrate near • In the initial stages, both forms of the disease
the molar-premolar area and if lower border produce unilocular or multilocular radio-
of the mandible is involved, there is often lucent areas in the bone containing faint bony
presence of a bulging and an increase in the trab aculae (Fig. 15.8).
depth of the jaw.
• The disease often produces expansion and
• Larger lesions may sometimes become trau- distortion of cortical plates of bone with
matized and ulcerated due to impingement displacement of teeth.
by the teeth during chewing.
• Sometimes ‘egg-cell’ crackling of the expan-
• The polyostotic type of fibrous dysplasia ded cortex of the affected bone may be seen.
causes gross swelling and deformity in
multiple numbers of bones, with pain and • Later on, as the lesion matures, a classical
sometimes pathological fractures. “ground glass” or “orange peel” or
“pebbled” appearance of bone is observed
• The polyostotic fibrous dysplasia with multi- in radiographs and ground glass type is the
ple bone involvement and skin “café-au-lait” most common radiographic appearance of
pigmentation but without any endocrine fibrous dysplasia.
disturbances is known as Jaffe-Lichtenstein
syndrome.

• The “café-au-lait” skin pigmentations are
characterized by light-brown pigmented
areas over the skin, which has a typical jagged

Diseases of Bone 485

Fig. 15.8: X-ray shows diffuse radiolucency • Mandibular lesions exhibit expansion of both
in mandible (Right side) buccal and lingual cortical plates with bulging

distortion of the lower borders.

• The inferior alveolar canal is often displaced

superiorly from its normal position due to the
expanding bony lesion.

• Both erupted and unerupted teeth are

randomly distributed within the lesion.

• Fibrous dysplasia often radiographically
exhibits narrowing of the periodontal ligament

space and an ill-defined lamina dura.

• Maxillary lesions present obliteration of the

maxillary sinus with superior displacement of
the sinus floor.
• Involvement of multiple skull bones, e. g.
occipital, frontal and sphenoid, etc. by the
disease along with the maxillary bone often
characteristically produces increased density
of the base of the skull.

Fig. 15.9: X-ray shows diffuse radiolucency Key points of fibrous dysplasia of bones
in mandible with multiple radiopacities
• Fibrous dysplasia is a fibro-osseous disorder, in
which an area of normal bone is gradually
replaced by abnormal fibrous connective tissue.

• The disease occurs in two main forms-
monostotic (when a single bone is affected) and
polyostotic (when multiple bones are affected).

• The disease causes progressive, painless, smooth,
swelling of the jaw with facial asymmetry.

• Polyostotic fibrous dysplasia may be associated
with McCune-Albright’s syndrome, which
presents multiple bone swelling, ‘café-au-lait’
skin pigmentations and precocious puberty, etc.

• On radiographs the disease produces a classical,
“ground glass” appearance of bone.

• Histologically, fibrous dysplasia exhibits a highly
cellular, well-vascularized fibrillar connective
tissue that replaces the normal bone.

• Multiple irregular, trabeculae of immature bone
are found within the fibrous tissue, typically
produce a “Chinese letter” pattern.

Fig. 15.10: Radiographic view of fibrous dysplasia LABORATORY FINDINGS

• The margin of the lesion is not well-demarcated • The serum calcium, phosphorus and alkaline
and it gradually blends imperceptibly with phosphatase levels are within normal limits.
the adjacent normal bone.
• Occasionally, there may be elevated serum
alkaline phosphatase levels in polyostotic form
of the disease.

• BMR may be moderately high.

486 Essentials of Oral Pathology

• Premature secretion of pituitary follicle feature particularly distinguishes fibrous
stimulating hormone may occur in some cases. dysplasia from ossifying fibroma of bone,
since the later lesion is well-demarcated from
HISTOPATHOLOGY (FIG. 15.11) the surrounding bone by a capsule).
• With increase in the age of the lesion, the
• Histologically fibrous dysplasia reveals the amount of cellularity within the fibrous tissue
presence of a highly cellular, proliferating, decreases and the amount of bone tissue
well-vascularized fibrillar connective tissue increases. This feature is more commonly
that replaces the normal bone. evident in the jaw lesions rather than the long
bone lesions.
• Within the fibrous tissue stroma, multiple • Progressive remodeling of the woven bone to
spindle-shaped, fibroblast cells of uniform lamellar bone is also commonly observed as
size, are arranged in a “whorled pattern” and the lesion matures.
moreover, the collagen fiber bundles • Occasionally, fibrous dysplasia of bone may
completely lack their orientation. be associated with the development of
aneurysmal bone cyst.
• Multiple coarse, irregular, trabeculae of
immature bone are distributed within the DIFFERENTIAL DIAGNOSIS
fibrous tissue and they typically produce a
“Chinese letter” pattern. These bony • Ossifying fibroma
trabeculae are formed due to osseous • Cementifying fibroma
metaplasia of the connective tissue stroma. • Paget’s disease of bone
• Garre’s osteomyelitis
• These bony trabeculae are evenly spaced, • Hyperparathyroidism.
uniformly distributed and are separated from
one another, the trabeculae are not bordered TREATMENT
by osteoblast cells as seen in the normal bone,
instead there may be few osteoblast cells Fibrous dysplasia is a self-limiting disease and
scattered throughout the bone trabeculae. the growth usually ceases after puberty, with
spontaneous bone remodeling. However,
• Spheroidal areas of calcification resembling surgical recontouring of bone may be needed in
cementum may be present within the lesion larger lesions for cosmetic or functional reasons.
and occasionally there may be presence of foci Fibrosarcoma may develop from these lesions,
of giant cells in the lesion. especially, following radiotherapy.

• In jaw lesions the bony trabeculae may be CHERUBISM
thicker and blunter than that of the long bone
lesions. DEFINITION

• Osteoblastic and osteoclastic activity may be Cherubism is a rare benign hereditary condition,
present in relation to some trabeculae of bone. being inherited as an autosomal dominant trait,
which affects only the jawbones. The disease is
• At the margin, the lesion gradually blends characterized by “bilaterally symmetrical
with the surrounding normal bone (this enlargement” of mandible or sometimes the
maxilla.

The entity Cherubism was first reported by
Jones in the year 1933.

Fig. 15.11: Photomicrograph of fibrous dysplasia of bone PATHOGENESIS

Cherubism is a hereditary disease, however,
according to many investigators it can occur as a
result of the following reasons:

Diseases of Bone 487

• Anomalous development of bone appreciate the abnormality unless the
• Latent hyperparathyroidism mandibular swelling becomes substantial.
• Hormone dependent neoplasm. • When the maxillary swelling is very extensive,
• Trauma pressure on the floor of the orbit may result in
• Disturbance in the development of bone an upward turn of pupils of the patient’s eyes
and thus revealing a rim of white sclera below
forming mesenchyme. the iris; this phenomenon is often referred to
as the “heavenward look”.
CLINICAL FEATURES This so called heavenward look often gives
patient an ‘angelic appearance’.
Age: The disease commonly affects the young • Moreover, the severe maxillary swelling in
individuals, usually at the age between 1 to 5 cherubism may cause stretching of the facial
years. skin and retraction of the lower eye-lids.
Sex: More common among males than females. • Patients with cherubism commonly exhibit
increased cheek fullness, expansion and
PRESENTATION widening of the alveolar ridge, flattening of
the palatal vault (Fig. 15.13).
• The disease follows a familial pattern and • On rare occasions there can be destruction of
several members of the same family may be the infraorbital ridge.
affected. Some non-familial cases are also • Non-inflammatory submandibular lympha-
reported, which occur due to new mutations. denopathy also develops in cherubism, which
occurs due to reactive hyperplasia.
• At birth the appearance of the patient is • Premature exfoliation of deciduous teeth,
absolutely normal. However, between the age extensive diastema formation and delayed
of 1 and 5 years a bilateral, painless, eruption of permanent teeth, etc. are often
symmetric swelling develops in mandible or associated with the disease.
sometimes in maxilla in severe cases (Fig. • Cherubism can also exhibit rotation or
15.12). transposition teeth and occasional resorption
of roots of teeth in the affected zone of the
• In cherubism, symmetrical mandibular jawbone.
swelling (which starts at the angle region on • The teeth are often irregularly arranged in the
both sides) along with excessive cheek fullness jaw or they may be displaced. Moreover,
often give rise to a typical appearance of hypodontia of the permanent teeth is common
“chubby face” to the child. in cherubism.
• In addition to facial deformity, random
• Since most little children naturally have a malalignment of teeth in the arch results in
somewhat chubby face, the parents may not malocclusion.

Fig. 15.12: Cherubism producing bilateral Fig. 15.13: Severe bony expansion in cherubism
mandibular swelling

488 Essentials of Oral Pathology

Key points of cherubism Fig. 15.14: Cherubism radiographically showing
multicystic radiolucency in mandible
• Cherubism is a rare benign hereditary condition
of the jaws, characterized by “bilaterally “cyst-like” radiolucent areas or cavities on
symmetrical enlargement” of mandible or both sides of mandible (Fig. 15.14).
sometimes the maxilla.
• The small radiolucent areas often coalesce
• The disease occurs at a very young age and together to from larger lesions defects in the
because of the large swelling of the facial bone bone.
the affected child typically has a “chubby face”.
• The initial destruction of bone starts at the
• Moreover the patient often has a so called angle of the mandible, which can be detected
“heavenward look” because of the upward turn by X-rays even before the clinical manifes-
of the pupil of the eye, this also gives an ‘angelic
appearance to the patient. tations of the disease start to appear.
• Cherubism in later stages causes severe
• Massive jaw swelling in cherubism can cause
gross facial deformity and malocclusion; which bilateral expansion of the jaw with thinning
lead to masticatory, swallowing, speech and even of the cortical plates.
breathing difficulties. • In few cases, there may be presence of the
classic ‘ground glass’ appearance in
• Radiograph in cherubism presents multiple cyst- cherubism.
like spaces in the jaw and sometimes multiple • Radiographs also reveal displacement of the
unerupted, teeth may look like just ‘floating’ inferior alveolar canal or obliteration of the
within these cysts. maxillary antrum in few cases.
• Sometimes, multiple unerupted and displaced
• Histologically the disease presents a highly teeth appear to be floating within the cyst-like
cellular and vascular connective tissue stroma, spaces and the condition is often referred to
containing numerous proliferating fibroblasts as ‘floating tooth syndrome’.
and variable numbers of multinucleated giant • Cortical perforations rarely occur and
cells. maxillary lesions often extend to the sinus.
• The radiographic changes in cherubism are
• The disease is self limiting and thus, no treatment often more overwhelming and extensive than
the actual clinical swelling produced by the
is required. disease.
• Interestingly, lateral skull radiographs often
• In severe cases of cherubism, the jaw swelling reveal exposure of the posterior part of the
can be so massive that the patients may have hard palate due to forward displacement of
masticatory, swallowing, speech and even the permanent teeth.
breathing difficulties.

• Compression of the cranial nerves may cause
visual and auditory disturbances in Cheru-
bism.

• Cherubism has been reported to occur in
conjunction with Noonan syndrome, which
is characterized by congenital heart disease,
chest deformity, mental retardation, facial
bone anomalies, webbed neck, gingival
fibromatosis, blood coagulation disorder and
obstructive sleep apnea, etc.

• The disease is at its peak during the age of 5
to 6 years, the bony growth usually becomes
static shortly after puberty and then it slowly
regresses.

RADIOLOGICAL FEATURES

• In cherubism, the involved jaw bone radio-
graphically shows well-defined, multilocular,

Diseases of Bone 489

Grading system in cherubism • In older lesions, the number of giant cells
decrease and the connective tissue becomes
According to Ramon and Engelberg, cherubism more fibrous.
lesions can be divided into the following grades
depending upon the extent and severity of the LABORATORY INVESTIGATIONS
disease process.
Serum alkaline phosphates levels are raised
Grade I Cherubism involving ascending ramus of during the osteoblastic phase (phase of repair)
mandible on both sides. of the disease.

Grade II Cherubism involving ascending ramus CT scans can be used to determine the extent
bilaterally along with both maxillary to which the disease has involved the jaw.

tuberosities. DIFFERENTIAL DIAGNOSIS

Grade III Massive involvement of whole maxilla • Fibrous dysplasia of bone
• Hyperparathyroidism
and mandible except the condylar • Caffey’s disease
processes. • Central giant cell granuloma
• Aneurysmal bone cyst
Grade IV Same as grade III with involvement of • Gorlin-Goltz syndrome.
floor of orbits causing orbital compres-
sion. TREATMENT

• Moreover, the radiographic defects in the bone No treatment is required since cherubism is a
may persist even after the disease had self-limiting disease and with skeletal maturation
clinically subsided. the disease regresses spontaneously after
puberty.
HISTOPATHOLOGY
OSTEOGENESIS IMPERFECTA
• Microscopic section from the lesion presents
a highly cellular and vascular connective Osteogenesis imperfecta is a genetically trans-
tissue stroma, which is often arranged in a mitted disease of bone characterized by defective
“whorled pattern”. matrix formation and lack of mineralization,
which results in an increased bone fragility.
• Numerous proliferating fibroblasts and
variable numbers of multinucleated giant PATHOGENESIS
cells are also found within the stroma.
The disease osteogenesis imperfecta occurs due
• Giant cells are relatively smaller in size and to failure of the fetal collagen (procollagen) to
they often aggregate around the thin walled transform into mature collagen (type I) through
blood capillaries. cross linking of adjacent molecules at the time of
formation of bone. These results in defective bone
• The number of giant cells gets fewer and fewer matrix formation along with failure of bone
as there is more and more spontaneous repair mineralization, leading to increased fragility of
of the bony defect. the bone tissue. In osteogenesis imperfecta the
bones grow to their normal length but are often
• A distinctive feature of the disease is the thin with lack of usual cortex formation as may
presence of an “eosinophilic perivascular be seen in a normal compact bone.
cuffing” of collagen fibers, which often
surrounds the blood capillaries. CLINICAL FEATURES (FIG. 15.15)

• Varying amounts of metaplastic bony tissues There are at least four types of osteogenesis
are found within the stroma. imperfecta, two of them are inherited as

• Within the connective tissue extravassated
blood and deposits of hemosiderin pigments
are sometimes seen.

• Lymph nodes exhibit reactive hyperplasia,
fibrosis and chronic inflammatory cell
infiltration.

490 Essentials of Oral Pathology

Severe Non-lethal Type

In this from of osteogenesis imperfecta, the disease
is not evident until the late childhood and the
patient shows fractures of bone with minimum
trauma. Sometimes the fractures may occur at
birth and the patients often have generalized bony
deformity. Although the fractured bone heals up
rapidly, considerable skeletal deformity and a
dwarfed stature often develop.

Fig. 15.15: Osteogenesis imperfecta Moderate and Deforming Type

autosomal recessive trait, while the other two are Patients in this type are less severely affected then
inherited as autosmal dominant traits. the other two types already mentioned. This type
of osteogenesis imperfecta may be associated
Interestingly, the recessive variants of the with dentinogenesis imperfacta (more in relation
disease are more severe in nature in comparison to deciduous teeth) and blue sclera in about 25
to the dominant variants. to 50 percent cases.

General clinical manifestations of osteogenesis These patients may also exhibit deafness,
imperfecta include the following: defective heart valves, joint dislocations,
• Bowing deformity of the bone with multiple abnormal muscular conduction, abnormal shape
of the skull, etc.
fractures due to increased fragility.
• Blue sclera with defective teeth in the form of The sclera appears blue because it is so thin
that the pigmented choroids become visible
‘bulbous crowns, dentinogenesis imperfecta through it.
and blue or brown translucency (opalescent
teeth)’. Mild Non-deforming Type
• Loss of hearing due to obliteration of the
cranial foramen with compression of nerve. This type of the disease occurs in nearly 60 percent
• Hypermobility of the joints. cases and the patients are clinically normal,
• Increased incidence of Class-III malocclusion although they have an increased tendency for
due to maxillary hypoplasia. bone fracture due to trauma. These patients also
• Excessive bruising tendency. have blue sclera and the associated dentino-
genesis imperfecta in about 25 percent cases.
TYPES OF OSTEOGENESIS IMPERFECTA
Oral manifestations of osteogenesis imperfecta
• Neonatal lethal type
• Severe non-lethal type • Large head size.
• Moderate and deforming type • Frontal bossing.
• Mild and non-deforming type. • Maxillary hypoplasia.
• Bulbous crowns of teeth with dentinogenesis
Neonatal Lethal Type
imperfecta and blue or brown translucence
This type of osteogenesis imperfacta is the most (opalescent teeth).
severe from of the disease (10%) and it is • Class III malocclusion with anterior and posterior
characterized by multiple fractures of bone in cross bite.
utero or during parturition and the child seldom • Severe attrition of deciduous teeth.
survives. • Multiple impacted permanent teeth.
• Excessive bruising tendency.
• Increased incidences of development of
osteitis and osteomyelitis following extraction of
teeth.

Diseases of Bone 491

RADIOLOGICAL FEATURES CLEIDOCRANIAL DYSPLASIA

Radiographically, osteogenesis imperfecta DEFINITION
reveals the following features:
• Shortened and deformed extremities with Cleidocranial dysplasia is a rare genetic disorder
characterized by abnormal growth of the bones
large areas of cyst-like radiolucencies. in clavicles, skull and the face with a tendency
• The midshaft areas are narrowed with for failure of tooth eruption.

bulbous metaphyseal–epiphyseal zones. ORIGIN
• Multiple fractures or healed areas of previous
The disease may be hereditary in nature with
fractures are often present in the bone. autosomal dominant trait or it may occur as a
• The teeth exhibit features of dentinogenesis result of spontaneous mutations.

imperfecta with bulbous crowns, obliteration CLINICAL FEATURES
of pulp chamber and short roots.
• Radiolucent or mixed ‘radiolucent-radio- • There may be complete absence or hypoplasia
paque’ lesions are found in the mandible with of one or both clavicles with hypermobility of
extreme thinning of the cortex. the shoulder joints and it is the most important
• ‘Warmin bones’ in the skull characterized by feature of cleidocranial dysplasia.
multiple small sutural bones in the skull
arranged in a mosaic pattern. • The disease affects both sexes equally.
• Interestingly, the patient can move their
HISTOPATHOLOGY
opposing shoulders medially up to the
• Severe form of osteogenesis imperfacta midline due to partial or complete absence of
histologically reveals thinning of the cortex, the clavicles and weakness of the muscles
which is composed of immature woven attached to them.
bone. • Frontal and parietal skull plates are elongated
(bossing), although the other bones of the
• Bony trabeculae are short, thin, and fragile and skull are normal.
they are widely spaced and disorganized.
Key points of cleidocranial dysplasia
• Bony tissue displays increased number of
osteoblasts with severely reduced bone • Cleidocranial dysplasia is a rare genetic disorder
matrix characterized by abnormal growth of clavicles,
skull and the face with a tendency for failure of
• The immature woven bones do not transform tooth eruption.
into mature lamellar bones.
• Due to abnormal development of clavicles,
PATHOGENESIS patient can often move their opposing shoulders
medially up to the midline.
The disease develops due to failure of the fetal
collagen to transform into mature collage • Patients also have short stature, big head, frontal
through cross-linking of adjacent molecules. This bossing, delayed closure of fontanels, etc.
results in a defective bone matrix formation with
increased fragility. • Oral manifestations of the disease include
hypoplasia of the jaws and multiple impacted or
TREATMENT unerupted supernumerary teeth.

No treatment is possible to alter the course of the • Radiograph reveals partial or complete loss of
disease. Some improvements in the condition clavicles, warmin bone in the skull with open
occur automatically after puberty. Care should fontanels and multiple impacted teeth in the jaw.
be taken during extraction of tooth, so that
alveolar bone is not fractured. • Patients often have short stature, big head,
long neck and narrow shoulders, etc.

• Delayed closures of the fontanels, underdeve-
loped paranasal sinuses, ocular hypertelorism

492 Essentials of Oral Pathology

and photophobia, etc. are the other important • Ascending ramus of the mandible is narrow.
features of the disease. • There may be hypoplasia of the alveolar

ORAL MANIFESTATIONS process.

• Entire mid-face is underdeveloped with HISTOPATHOLOGY
retrusion maxilla and decreased lower facial
height. The permanent teeth have no cellular cementum.

• Nose is flat, broad based and lacks the bridge. DIFFERENTIAL DIAGNOSIS
• Although, the mandible is of normal size, it
• Craniofacial dysostosis
appears elongated because of the hypoplastic • Cleidocranial dysostosis.
maxilla.
• High and narrow arched palate is almost TREATMENT
always seen with increased incidences of cleft
palate. No treatment is possible.
• In the oral cavity multiple embedded and
impacted permanent teeth are often present. OSTEOPETROSIS
• Large numbers impacted supernumerary (MARBLE BONE DISEASE)
teeth are also found in the jaws, which exhibit
defective crowns and abnormal root patterns. DEFINITION
• Patients of cleidocranial dysplasia often
exhibit multiple retained deciduous teeth with Osteopetrosis is an uncommon hereditary
delayed eruption of permanent teeth. disorder of bone characterized by abnormal
• Roots of the teeth are often thin and short, increase in the bone density due to absence of
moreover there may be absence of cellular physiologic bone resorption. The disease occurs
cementum on the roots. due to reduced osteoclastic activity in the bone,
• Development of partial or complete anodontia which results in increased solidification, extre-
may be seen in few cases. mely high density along with increased fragility
• Cystic lesions (especially dentigerous cysts) of the affected bone.
may develop in the jaws, mostly in association
with the impacted or embedded teeth. TYPES
• Cleidocranial dysostosis is another
condition, which is almost similar to the • Autosomal dominant—benign type (Adult
cleidocranial dysplasia and the only osteopetrosis).
difference between them is the presence of
normal clavicles in the former. • Autosomal recessive—malignant type
(Infantile osteopetrosis).
RADIOGRAPHIC FEATURES
PATHOGENESIS
• Tortuous suture lines in the skull bones
(warmin bones) with open fontanels and open The pathogenesis involves genetic defects charac-
sutures. terized by loss of normal balance between bone
formation and bone resorption in the skeleton. In
• Partial or complete loss of clavicles. this disease the bone deposition by the osteoblast
• Multiple unerupted and impacted teeth in the cells is normal, however the bone resorption and
remodeling by the osteoclast cells is completely
jaws, some of which are deciduous and some lacking; this often results in the formation of
are supernumerary teeth. hypermineralized, inelastic, solid bones with
• Roots of the teeth are thin and lack cellular profound tendency for fracture. The medullary
cementum deposition. cavities of bone are obliterated due to uninter-
• Maxillary sinus is small and rudimentary. rupted bone depositions and the epiphyseal end
plates of bone often appear club-shaped. There is
also lack of resorption of the calcified cartilages
during the endochondral growth.

Diseases of Bone 493

CLINICAL FEATURES • Decreased bone marrow activity often leads
to leucopenia and thrombocytopenia, which
• In osteopetrosis, the abnormalities in the bone can cause spontaneous hematoma formations
often results in altered sutures, compression and multiple infections in the bone (especially
odontogenic infections).
of cranial nerves and frequent fractures, etc.
• Decreased bone marrow hemopoetic func- • Osteomyelitis frequently develops following
tooth extraction.
tions with increased tendency for the deve-
lopment of severe osteomyelitis of the jaws are RADIOLOGY
also common. In osteopetrosis, radiographs often show the
• The infants suffering from malignant version classical feature of “bone within the bone
of this disease generally have osteopetrosis at appearance”. It results from increased thickening
birth or in the early childhood and they rarely of the cortex and obliteration of the medullary
survive longer. spaces of bone. Radiographs of the jawbone
• Most of the patients develop anemia, exhibit increased radiodensity of the bone, which
thrombocytopenia and leucopenia, etc. which is almost equal to that of the tooth.
occur due to decreased hemopoiesis because
The cartilaginous portions of the rib also
of lack of marrow (as the medullary space is exhibit an uncharacteristic increase in the
often completely obliterated by abnormal opacity.
bone deposition).
• Patients often have broad face, hypertelorism Cranial bones appear thickened and sinus
and snub nose, etc. cavities are reduced in size.
• Loss of function of bone marrow results in
compensatory extramedullary hemopoiesis DIFFERENTIAL DIAGNOSIS
within the liver and spleen, which often • Endosteal hyperostosis
results in hepatosplenomegaly. • Van-Buchem disease
• Patients often suffer from deafness, blindness, • Sclerosteosis
pain and facial paralysis, etc. due to narrowing
of the cranial foramina and the resultant HISTOPATHOLOGY (FIG. 15.16)
Microscopy shows a very dense and sclerotic
compression of nerves. bone with little compensatory remodeling.
• Enlarged cranium, frequent bone pain and
The medullary cavities are small and they
prominent frontal bossing, etc. are also contain very little amount of marrow tissue and
frequently seen. large amounts of amorphous bone.
• Long bones are often shortened and are
extremely fragile. Fig. 15.16: Photomicrograph of osteopetrosis
• Severe cases of osteopetrosis results in
breathing and hearing difficulties due to
oversized facial bones and mastoid process.
• The teeth often have defective enamel and
short roots. Their eruption process can be
delayed.

• There can be increased incidence of dental
caries and many of the teeth in the dental arch
can be ankylosed.

• Increased bone density and fragility may
cause frequent fractures of jawbone and
subsequent osteomyelitis following tooth
extractions, these occur due to decreased
blood supply to the bone along with increased
susceptibility to infections.

494 Essentials of Oral Pathology

In the bone marrow, osteoblasts are present • Jaw lesions of osteoma cause facial deformity
in normal numbers, but the osteoclasts are almost and difficulty in mouth opening.
absent.
• Multiple supernumerary teeth, impacted teeth
In some cases, normal number of osteoclast and odontomas frequently develop in the jaw.
cells may be present in the bone, but these cells
are not functionally viable. • Patients may have desmoid tumors of the soft
tissue and dermoid cysts of the skin.
TREATMENT
• Pigmented lesion in the ocular fundus is an
No treatment except bone marrow transplanta- important clinical finding of Gardner
tions. Supportive therapies like repeated blood syndrome.
transfusions and antibiotics are essential for the
survival of the patient. • The intestinal polyps may undergo malignant
transformation and develop invasive adeno-
PIERRE ROBIN SYNDROME carcinomas. Patients also have an increased
tendency for developing thyroid cancer.
Pierre Robin syndrome is a hereditary disorder,
characterized by the following features: TREATMENT
• Development of mandibular micrognathia,
Prophylactic colonectomy, surgical removal of
which results in a characteristic “bird facies” osteomas and the dermoid cysts.
of the patients.
• ‘U’ shaped cleft palate and glossoptosis MARFAN’S SYNDROME
(dropping of the tongue).
• Micrognathia in this disease often leads to the DEFINITION
downward and backward displacement of
tongue, which often results in breathing Marfan’s syndrome is a hereditary disease
trouble. transmitted or inherited as autosomal dominant
• Patients often have malocclusion of the teeth trait and is characterized by defective organi-
in association with multiple missing teeth or zation of collagen.
sometimes many supernumerary teeth.
• Absence of temporomandibular joint, mongo- CLINICAL FEATURES
lism, congenital heart defects, hydrocephaly, (FIGS 15.17 AND 15.18)
microcephaly and mental retardation, etc. are
the other important features of the disease. • The classic clinical finding in this disease is
• Difficulty often occurs in terms of feeding and the presence of abnormally long, thin extre-
maintenance of airway during infancy. mities and spidery fingers (Fig. 15.18).
• Psychological trauma is often associated with
this syndrome due to abnormal appearance • Patients are usually very tall and slim, and
and speech difficulty. they often have muscle hypotonia.

• The patients often show hyperextensibility of
joints, with recurrent habitual dislocations,

GARDNER SYNDROME

It is a hereditary disorder characterized by
colorectal polyps in association with various
other lesions involving the skin, eyes, teeth and
the skeletal system, etc.

CLINICAL FEATURES Fig. 15.17: Marfan’s syndrome-I

• Multiple intestinal (colorectal) polyps, multi-
ple osteomas of the skin, paranasal sinuses and
jaws (preferably mandible).

Diseases of Bone 495

DIAGNOSIS
By determination of upper and lower segment
ratio and the metacarpal index.

TREATMENT
No treatment.

Fig. 15.18: Marfan’s syndrome-II DOWN SYNDROME (TRISOMY 21)

frontal bossing, large external ears and Down syndrome is the most common chromo-
shrunken eyes, etc. somal abnormality to occur in man. There are
• Many of the patients also develop kyphosis, many forms of the disease but the most common
scoliosis and flat foot, etc. one is trisomy 21 (about 94%), which is caused
• Cardiac abnormalities like aortic aneurysm, by the chromosomal non-disjunction, thereby
aortic regurgitation and valvular defects, etc. resulting in an extra chromosome with the
are also commonly associated with this chromosome pair of 21.
disease.
The down syndrome of trisomy 21 type
ORAL MANIFESTATIONS (FIG. 15.19) involves almost all organs of the body and it
affects the child more often, if the maternal age
• Patients often have a long and narrow face, is above 45 years.
bifid uvula, cleft palate and high palatal vault.
CLINICAL FEATURES (FIGS 15.20 AND
• Malocclusion of teeth, temporomandibular 15.21)
joint (TMJ) dysarthrosis.
• Patients with Down syndrome present a
• Increased chances of development of variety of defects like–short stature, flat face,
multicystic lesions in the jawbone. depressed nasal bridge and small slanting
eyes with epicanthral folds (features of typical
DIFFERENTIAL DIAGNOSIS mongoloid facies) (Fig. 15.20).

• Sickle cell anemia • Mental retardation, large anterior fontanel,
• Klinefelter’s syndrome open cranial sutures, small ears and sexual
• Homocystinuria. underdevelopment, etc. are often present.

Fig. 15.19: Marfan’s syndrome-III Fig. 15.20: Typical facial profile of Down syndrome

496 Essentials of Oral Pathology

TREATMENT
No treatment is required.

INFANTILE CORTICAL HYPEROSTOSIS
(CAFFEY’S DISEASE)

DEFINITION

Caffey’s disease is a perplexing anomaly of
unknown etiology and it is characterized by an
abnormal enlargement of bone in children, along
with other systemic complications.

Fig. 15.21: Intraoral picture of Down syndrome TYPES
showing no remarkable abnormality
Two types—familial and sporadic, the familial
Oral manifestations of Down syndrome type arises usually earlier than the sporadic
type and some lesions can be present even at
• Short head, small and open mouth with protrution birth.
of tongue due to macroglossia.
CLINICAL FEATURES
• High-arched palate, hypoplastic maxilla.
• Mandibular prognathism with class III • Most of the patients are below 6 months of
age and in few cases it may even develop in
malocclusion, delayed eruption of teeth. the intrauterine life.
• There may be presence of cleft lip or palate with
• Patients often exhibit rapidly developing,
difficulty in speech. bilaterally symmetrical mandibular swelling,
• Tongue is generally large (macroglossia), it is which disappears in 3 to 12 months. However,
the disease should not be confused with
pebbly and fissured (scrotal tongue). cherubism, which also presents bilateral
• Lips are often thick, everted, dry and fissured mandibular swelling.

with presence of angular cheilitis. • There may be presence of few deep-seated,
• Malocclusion, partial anodontia and microdontia tendered, soft tissue swellings.

with short roots of teeth. • The patients are often highly irritable and are
• Malformed teeth, taurodontism, supernumerary unable to take food, and they may also have
fever, leukocytosis, raised ESR and elevated
teeth and enamel hypoplasia, etc. are frequently serum alkaline phosphatase levels, etc.
seen.
• Low caries activity. • Dysphagia, pseudoparalysis, anemia and
• These patients may have an increased tendency leukocytosis often occur.
to develop acute necrotizing ulcerative gingivitis
(ANUG) and juvenile periodontitis. • Soft tissue swellings usually develop in those
• Gross plaque accumulations. areas of the body from where hyperostosis of
• Bruxism. the bone occurs in future.
• Poor muscle tone.
• Increased susceptibility to infection. Oral manifestations

• Patients often have broad and short hands • Frequent mandibular bone involvement with
with small feet and digits, protuberant deformity and facial swelling.
abdomen and delayed puberty, etc.
• Soft tissue or muscle swelling of the face.
• These patients often have heart anomalies
(40 percent cases), moreover they come in • Difficulty in swallowing.
the higher risk category for development
of leukemia and Alzheimer-like dementia • Refusal of food by the child.
in later life.
• Malocclusion of teeth.
• The iris shows brushfield spots.

Diseases of Bone 497

RADIOGRAPHIC FEATURES Patients often have a down turned mouth with
presence of lateral facial clefts.
Radiographically, the disease exhibits abnormal
thickening of mandibular cortical bone and Important oral manifestations of this disease
bulging of its lower border due to subperiosteal include crowding and malocclusion of teeth, high
new bone formation. The sub-periosteal new arched palate and occasional clefts, etc.
bone formation with cortical thickening is often
known as periosteal cloaking. Atypical hair growth in the form of ‘tongue
shaped” hairline.
HISTOPATHOLOGY
Parotid hypoplasia.
Microscopy reveals edema and thickening of the Narrowing of larynx and trachea combined
periosteum, with apposition of many thin bony with mandibular hypoplasia often causes
trabeculae parallel to one another. respiratory and speech difficulties in children.

DIFFERENTIAL DIAGNOSIS RADIOGRAPHIC CHANGES

• Osteomyelitis Radiographs reveal partial or complete agenesis
• Osteoma of mandible and malar bones with small para-
• Abnormally healed fractured bone nasal sinuses.
• Cherubism
• Osteopetrosis. TREATMENT

No treatment is required.

TREATMENT ACHONDROPLASIA

No surgical intervention is required and prog- DEFINITION
nosis is good. Steroids may be given to eliminate Achondroplasia is the hereditary defect of endo-
the symptoms. chondral ossification.

MANDIBULOFACIAL DYSOSTOSIS CLINICAL FEATURES
(TREACHER-COLLINS SYNDROME)
• Patients with achondroplasia often exhibit
Mandibulofacial dysostosis is rare hereditary dwarfism, short and muscular extremities,
or familial disease characterized by defects in bowed legs and large head, etc.
the structures derived from 1st and 2nd
branchial arches. The disease often shows • The limbs are extremely short in relation to the
multiple closely related defects of the head and trunk and head. Dwarfism in achondroplasia
face area. occurs due to failure of normal cartilage
proliferation at the epiphysis, which results in
CLINICAL FEATURES failure of longitudinal growth of the long bones.

Malformation of the external ear (distorted • The short-limbed dwarfs of achondroplasia
pinna) with absence of external auditory canal, traditionally become circus clowns.
there is occasional deformity in the middle and
internal ear. • The insufficient growth at the base of the skull
causes retrusive mid-face development with
Antimongoloid palpebral fissures with a concave profile.
coloboma of the outer portion of the lower eye
lids. • Oral manifestations of this disease include
short maxilla, depressed nasal bridge, relative
Marked hypoplasia of the mandibular body mandibular prognathism and malocclusion,
and zygoma with narrow face and depressed etc.
cheek.
RADIOLOGICAL FINDING
All these facial changes give the patient a
typical “bird-face” or “fish-face” like appea- Radiographs reveal long bones, which are shorter
rance. than normal with thickening of the ends.
Maxillary retrusion is also seen.

498 Essentials of Oral Pathology

Typical radiological features of some bony lesions

• Paget’s disease of bone Cotton-wool appearance.

• Fibrous dysplasia of bone ‘Ground glass’ appearance.

• Ameloblastoma ‘Soap bubble’ or ‘honey comb’ appearance.

• Cherubism Multiple cyst-like radiolucency often occurs in mandible bilaterally.

• Osteogenesis imperfecta Deformity of bone, narrow mid shaft and bulbous metaphyseal and
epiphyseal ends and multiple fractures.

• Osteopetrosis ‘Bone within the bone’ appearance.

• Infantile cortical hyperostosis Abnormal thickening of mandibular bony cortex with bulging of the
lower border.

• Osteosarcoma Sun-ray or sun-burst appearance.

• Myxoma Tennis racket appearance.

• Multiple myeloma Multiple ‘punched-out’ radiolucency.

• Carcinoma ‘Moth-eaten’ appearance.

• Carcinoma of maxillary antrum ‘Clouding’ of the antrum.

• Pindborg’s tumor ‘Driven-snow’ appearance.

• Thalassemia ‘Hair on end’ or ‘crew cut‘ appearance of skull bone.

• Garre’s osteomyelitis ‘Onion skin’ appearance and ‘duplication of cortex’ of bone.

• Cleidocranial dysplasia ‘Warmin bone’ and multiple unerupted or impacted teeth.

• Dentigerous cyst Well-defined unilocular radiolucency enclosing the crown of an
impacted tooth.

• Radicular cyst Well-defined radiolucency at the root apex of a non-vital tooth.

• Nasopalatine duct cyst A ‘heart shaped’ radiolucency in the anterior palate.

• Globulomaxillary cyst ‘Inverted pear’ shaped radiolucency.

• Hyperparathyroidism Multiple cyst-like radiolucency of bone, ‘salt and pepper’ effect on
lateral skull radiograph.

• Osteoarthritis of TM joints Osteophytic lipping and occasional ‘Ely’s cyst’.

• Peripheral giant cell granuloma ‘Peripheral cuffing’ of bone.

• Central giant cell granuloma ‘Soap-bubble’ type multilocular or ‘drop- shaped’ unilocular
radiolucency.

• Compound odontome Multiple miniature tooth-like structures projecting from a single
focus.

• Cementoblastoma A large radiopaque mass associated with a tooth root surrounded by a
thin zone of radiolucency.

HISTOPATHOLOGY MASSIVE OSTEOLYSIS
(VANISHING BONE DISEASE)
Microscopically, the affected bone reveals
retardation of endochondral growth and non- DEFINITION
replacement of the cartilage by the normal
bone. It is an uncommon and unusual disease charac-
terized by sudden, spontaneous and massive
TREATMENT resorption of bones leading to their complete
disappearance and subsequent replacement by
No treatment is possible. Malocclusion can be fibrous tissue.
corrected with orthodontic treatment.

Diseases of Bone 499

CLINICAL FEATURES TREATMENT
Radiation therapy may prevent the progression
Age: Teen age and young adults. of the disease, otherwise there is no successful
treatment.
Sex: Commonly affected bones by the disease are
clavicle, scapula, humerus, ribs and sacrum, etc. Typical radiological features features of some
any lesion.
Among the jawbones, mandible is more
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• The disease is spontaneous and asympto-
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current concepts in pathogenesis and treatment.

DEVELOPMENTAL ETIOLOGY
DISORDERS The condition develops probably due to some
localized proliferative reactions in the jawbone,
HYPOPLASIA OF THE MANDIBULAR which are as follows:
CONDYLE • Osteomyelitis
• Middle ear infection
Condylar hypoplasia is characterized by reduc- • Infection in the infratemporal fossa
tion in the size of condylar process. • Overactivity of the condylar cartilage
• Gigantism
ETIOLOGY • Acromegaly
• Paget’s disease, etc.
• Heredity
• Birth injury CLINICAL FEATURES
• Infections to the adjoining structures The clinical features of condylar hyperplasia
• Developmental anomalies, e.g. Treacher include deviation of chin to the opposite side
during mouth opening, cross bite, excessive
Collin’s syndrome, hemifacial microstomia, vertical lengthening of the ramus and occasional
etc. pain in the TMJ, etc.

CLINICAL FEATURES DIFFERENTIAL DIAGNOSIS
Osteochondroma.
• Underdevelopment of ramus.
• Deviation of mandible to the affected side TREATMENT
The condition is treated by surgical recontouring
during mouth opening. of the condyle.
• Antigonial notch is deeper on the involved
TRAUMATIC DISORDERS
side.
• Midline shift of dentition towards the affected

side.
• Masticatory insufficiency
• Cosmetically poor appearance of the face

TREATMENT LUXATION AND SUBLUXATION
Genioplasty or osteotomy.
Luxation or dislocation of TMJ occurs when the
HYPERPLASIA OF THE MANDIBULAR head of the condyle moves anteriorly over the
CONDYLE articular eminence into such a position from
where it cannot return back to its original
Condylar hyperplasia is a rare defect, which is position by itself.
often characterized by a unilateral enlargement
of the mandibular condyle with facial When the condyle is completely dislocated, it
asymmetry. is called luxation, while the partial dislocation
of the same is called subluxation.

Diseases of Temporomandibular Joint 503

ETIOLOGY ANKYLOSIS OF TEMPOROMANDI-
BULAR JOINT
Luxation or subluxation occurs mostly due to:
• Trauma to the TMJ. Ankylosis of the TMJ is characterized by lack of
• Wide mouth opening for an extended period movement of the condylar head within the
glenoid fossa, due to fusion of the opposing
of time (e.g. dental procedures, etc.). components of the joint with obliteration of the
joint space. It results in the limitation of mouth
CLINICAL FEATURES opening.

The patients usually complain of “sudden ETIOLOGY
locking” of the jaw with inability to close the
mouth. In the initial phases, the problem happens A large number of factors can cause the develop-
rarely, but later on, patients may have such ment of TMJ ankylosis and important among
situation quite frequently, thereby, making them are as follows:
eating and talking very difficult.

TREATMENT CLINICAL FEATURES
Age: Ankylosis usually occurs in children below
In case of luxation or subluxation, the dislocated the age of 10 years.
condyle is to be guided into its normal position Sex: Both sexes are almost equally affected.
by giving inferior and posterior pressure while
holding the mandible firmly in the molar region. TYPES OF ANKYLOSIS
False ankylosis: False ankylosis is extra-articular
Patients should be advised not to open the and it occurs due to fibrous or bony union
mouth too widely. In recurrent cases, flattening
of the articular eminence is done.

Trauma Etiology of ankylosis of TMJ

Infections • Birth injury due to forceps delivery.
Systemic juvenile arthritis • Intracapsular fracture with bleeding.
Neoplasms • Accidental trauma to the mandible that pushes the
Miscellaneous
head of the condyle into the glenoid fossa.
• Lack of early mobilization after TMJ fracture.
• Malunion of the condylar fractures.
• Radiotherapy to the TMJ.

• Otitis media.
• Mastoiditis.
• Congenital syphilis.
• Osteomyelitis.
• Pyogenic arthritis of TMJ from hematogenous infections.

• Psoriatic arthritis.
• Osteoarthritis.
• Rheumatoid arthritis.

• Chondroma.
• Osteochondroma.
• Osteoma.
• Metastatic tumors.

• Congenital developmental defect in the joint.
• Synovial chondromatosis.

504 Essentials of Oral Pathology

between the coronoid process and maxilla or Fig. 16.2: Ankylosis of TM joint causing microstomia
zygoma. Here the joint itself is not deformed or
damaged. • Maximum numbers of ankylosis cases are of
unilateral type, patients exhibit displacement
True ankylosis: True ankylosis is intra-articular of chin (backwards and laterally) towards
and it is again of two types: the involved side on attempted mouth
opening.
True bony ankylosis: When the TMJ space is
completely obliterated by the deposition of bone • Ankylosis causes retrusion of mandible with
following destruction and subsequent fusion of increased over jet of teeth.
temporal fossa, meniscus and head of the
condyle, the condition is called a true bony • Bilateral ankylosis in the younger age causes
ankylosis and in such cases complete loss of microstomia and receding chin.
mouth opening results.
• Occasionally, the patient may complain of
True fibrous ankylosis: Intra-articular fibrous pain and tenderness in the TMJ area.
ankylosis occurs, if the TMJ space is obliterated
by the deposition of a fibrous tissue mass (e.g. RADIOLOGICAL FEATURES
scar). In such cases, limited degrees of mouth
opening are possible. Fibrous ankylosis occurs In case of bony ankylosis, radiograph shows the
due to hemorrhage in the joint space due to loss of normal architecture of TMJ and oblitera-
trauma with subsequent fibrosis (hemarthosis). tion of the joint space due to deposition of bone.
In case of false ankylosis the TMJ appears normal
PRESENTATION (Fig. 16.3).

• Mostly seen in young people and both sexes
are equally affected.

• Difficulty in mouth opening is the chief comp-
lain in TMJ ankylosis, patients can open the
mouth partly in case of fibrous ankylosis, but
in case of bony ankylosis complete lack of
mouth opening is seen (Fig. 16.1).

• Microstomia with severe malocclusion
(Fig. 16.2).

• Difficulty in taking food and difficulty in
speech.

Fig. 16.1: Ankylosis of TM joint with complete Fig. 16.3: Ankylosis of TM joint showing
lack of mouth opening obliteration of the joint space

Diseases of Temporomandibular Joint 505

HISTOPATHOLOGY OSTEOARTHRITIS

Microscopically the ankylosed joint shows Osteoarthritis is a degenerative and destructive
destruction of the component parts of TMJ, e.g. disease of the weight-bearing joints, although
head of the condyle, meniscus and the fossa, etc. TMJ is not a weight-bearing joint, osteoarthritis
The joint space is completely filled up with either can still occur in it due to the ageing process or
fibrous tissue or by bone. trauma.

TREATMENT CLINICAL FEATURES

TMJ ankylosis is treated by surgical correction Clinically, osteoarthritis presents the following
of the joint (arthroplasty). Moreover to eliminate features:
further possibility of ankylosis or recurrence, a • Clicking sounds in the joint while opening and
gap is constantly maintained between the head
of the condyle and the glenoid fossa, by placing closing movements of the jaw.
some non-absorbing material, e.g. tendon sheath, • Limitation of movements of the joint.
in the joint space. This procedure is known as • Sometimes there may be deep ache or pain in
“gap arthroplasty”.
the joint.
Costochondral grafting is done sometimes in • Muscles of mastication are often tendered due
young patients to facilitate the growth of
mandible. to strain caused by non-use or restricted use
of the painful joint.
INFLAMMATORY DISORDERS
RADIOGRAPHIC FEATURES
ANKYLOSING SPONDYLITIS
Radiograph shows “osteophytic lipping” or pro-
Ankylosing spondylitis is a chronic inflamma- truberance on the articular disc with flattening
tory disease of the connective tissue, which of the articular surfaces of the joint.
primarily affects the axial skeleton and the central
joints including the TMJ. In few cases, subarticular radiolucent areas
(Ely’s cysts) can be seen.

Narrowing of the joint space due to abnormal
ossifications.

ETIOLOGY OTHER INVESTIGATIONS
• CT scanning
• Exactly not known. • Arthroscopy
• Trauma and rheumatoid arthritis could cause • MRI.

this disease.

CLINICAL FEATURES HISTOPATHOLOGY
• Stiffness resulting from immobility of the joint
• Osteoarthritis histologically shows vertical
during sleep. and horizontal cracks on the articular
• Stiffness is relieved by heat and exercise. It is cartilage. In more chronic cases these cracks
may even extend up to the underlying bone.
more common in men and there may be some
facial asymmetry. • The cartilage also becomes less elastic with
decrease in the number of chondrocytes.
RADIOGRAPHIC FEATURES
Flattening of the condyle with presence of • Degeneration of chondrocytes, localized
osteophytes, bony erosion and sclerosis. destruction of cartilage and eubernation of
bone, etc. are also seen.
TREATMENT
Intra-articular injections of corticosteroids. • Large degenerating spaces or sub-chondral
cysts may develop beneath the articular
cartilage.

506 Essentials of Oral Pathology

• In few cases, localized areas of repair produce have taken place in the meniscus and the
multiple elevations on the disk surface and the articular cartilage.
condition is known as “lipping”. • There may be presence of salivary gland
swelling and dryness of mouth.
• The bone beneath the joint cartilage shows • On rare occasions, rheumatoid arthritis
reduced osteoblastic or osteoclastic activity patients may develop secondary Sjogren’s
with fatty degeneration of the marrow. syndrome.
• In cases of rheumatoid arthritis in children
TREATMENT (Still’s disease), restricted jaw movements may
cause mandibular underdevelopment with
There is no satisfactory treatment for osteoarthri- concomitant occurrence of class II division I
tis, however condylectomy should be considered malocclusion.
in very severe cases. • Ankylosis of the TMJ may develop on rare
occasions due to rheumatoid arthritis.
RHEUMATOID ARTHRITIS
RADIOLOGY
Rheumatoid arthritis is a systemic disease that
usually affects many joints including the TMJ and Radiograph shows irregularity of the condylar
the disease is characterized by progressive as well as the articular surfaces, with flattening
inflammatory destruction of the joint structures. of condyle and widening of TMJ space.

ETIOLOGY HISTOPATHOLOGY
Detection of increased serum IgG, rheumatoid
factor and antinuclear antibodies, etc. indicate • Microscopy reveals edema, exudation and
that an “autoimmune mechanism” probably other inflammatory changes within the
initiates the disease. The autoimmune reaction synovial membrane of the joint.
brings about inflammatory change in the
synovial membrane of the joint with subsequent • The articular surface is ultimately destroyed
fibroblastic proliferations. The inflammatory and is replaced by the granulation tissue.
process also generates collagenese and other
enzymes, which cause destruction of the joint • Chronic inflammatory cell infiltration by
cartilage and the underlying bone. lymphocytes, macrophages and neutrophils
is often seen in the damaged tissue of the
CLINICAL FEATURES joint.
• The disease usually occurs in the third and
• There can be development of fibrous or even
forth decade of life and females are more bony ankylosis of the joint in some cases.
commonly affected.
• During the acute phase of the disease, patient TREATMENT
may suffer from fever, malaise, fatiguability,
weight loss, anemia and raised ESR, etc. Systemic steroid therapy and antibiotics.
• The TMJ is involved mostly bilaterally along
with other joints. ACUTE TRAUMATIC ARTHRITIS
• It becomes swollen, tendered and stiff.
• The maximum feeling of stiffness is Acute traumatic arthritis occurs due to trauma
experienced in the early mornings and it to the mandible, which results in inflammatory
diminishes gradually as the day progresses. changes within the TM joint space. It may also
• There may be occasional presence of pain, occur due to hemarthrosis, in case blood vessel
crepitations and tenderness in the joint, is torn inside the joint.
resulting in restricted jaw movements.
• Clicking sounds in the joint may develop in CLINICAL FEATURES
chronic cases, where structural alterations
• Pain and tenderness in the joint.
• Inability to close the mouth completely.
• Pain increases while opening and closing the

mouth.

Diseases of Temporomandibular Joint 507

TREATMENT • In many cases, the pain radiates to the angle
of mandible or temporal region.
Giving adequate rest to the joint and application
of heat. Mobilization of the joint after ten days. • The intensity of pain varies at different times
of the day.
MYOFACIAL PAIN DYSFUNCTION
LABORATORY INVESTIGATIONS
(MPD) SYNDROME
• Complete blood count (CBC) to rule out any
Myofacial pain dysfunction syndrome is a systemic infection.
disease complex that disturbs the entire masti-
catory apparatus and is characterized by pain • ESR, Rheumatoid factor (RF) and Antinuclear
and limitation of movement of the TMJ. antibody (ANA) are done to rule out possible
diagnosis of rheumatoid arthritis.
ETIOLOGY
• Serum uric acid should be checked to rule out
• The disease occurs due to defective neuro- the underlying disease ‘gout’
mascular coordinations coupled with emo-
tional stress, which eventually results in DIFFERENTIAL DIAGNOSIS
masticatory muscle spasm and fatigue.
• Referred pain from the nearby teeth.
• The condition is further aggravated by occlu- • Organic disease in the TMJ, e.g. inflammation
sal disharmonies like defective restoration,
lack of posterior occlusion due to loss of molar with fluid accumulation in the joint space.
teeth and faulty dentures, etc. • Trigeminal or glossopharyngeal neuralgia.
• Migraine.
• Habitual grinding of teeth (bruxism) can also
initiate the disease. TREATMENT

• Anxiety, stress and personality disorders The disease is self-limiting and does not progress
can play a major role in the initiation of the to any permanent disability or damage. Conser-
disease. vative treatment is often done by administering
analgesics, muscle relaxants and tranquilizers,
• Minor injury to the TMJ caused by violent etc. Besides this, correction of occlusal
yawning, laughing and strenous dental disharmonies, psychological counseling and
treatment of long durations. warm compress, etc. are also done.

CLINICAL FEATURES NEOPLASIA OF TEMPORO-
MANDIBULAR JOINT
• More than 80 percent of the patients are
females and they are usually aged between Both benign and malignant neoplasms can deve-
20 and 30 years. lop from the TMJ, but their incidence is usually
rare.
• The pain in this disease is dull in nature and
it is usually present unilaterally in the pre-
auricular area or in the ear.

Clinically four positive features and two negative features of MPD

Positive features Negative features

• Pain in the TMJ and adjacent areas. • Absence of any clinical, radiological and
• Muscle tenderness. biochemical evidence of organic change
• Limitation of movements and deviation in the joint.

of the jaw. • Absence of tenderness in the joint, when
• Clicking sounds in the TMJ during opening palpated through the external auditory
meatus.
and closing of the mouth.

508 Essentials of Oral Pathology

Common neoplasms of TMJ

Benign neoplasms Malignant neoplasms

• Osteochondroma • Chondrosarcoma
• Osteoma • Primary intrinsic malignant

• Chondroma neoplasms
• Fibromyxoma • Synovial sarcoma
• Giant cell lesions • Fibrosarcoma
• Chondromatosis

SITE OF ORIGIN 2. De Bont LGM. Temporomandibular joint, articular
Neoplasms of TMJ can occur from any structural structure and function. Rijksuniversiteit Groningen
components of the joint like head of condyle, 1985;1-83.
articular fossa, disc or the capsule, etc.
3. Gazit E, et al. Prevalence of mandibular function in 10-
CLINICAL FEATURES 18 year old Israeli school children. Journal of Oral
Neoplasms of TMJ can cause the following Rehabilitation 1984;11:307-17.
problems:
• TMJ dysfunctions 4. Ginhrass RO. Chondrosarcoma of the mandibular joint.
• Facial asymmetry Journal of Oral Surgery 1954;12:614.
• Malocclusion
• Prognathic deviation of mandible to the 5. Goss AN, Burns RJ. Facial pain. Australian Dental
Journal 1975;20:287-9.
opposite side.
• Pain and swelling. 6. Kummoona R. Functional rehabilitation of ankylosed
temporomandibular joints. Oral Surgery, Oral
TOMOGRAPHY Medicine and Oral Pathology 1978;46:495-505.
Malignant neoplasms can cause destruction of
the joint structures, which could be easily 7. Muir CM, Goss AN. The radiographic morphology of
detected by tomography. painful temporomandibular joints. Oral Surgery, Oral
Medicine and Oral Pathology 1990;70:355-9.
TREATMENT
It depends upon the specific nature of the 8. Norman JE, De B, Painter DM. Hyperplasia of the
lesion. mandibular condyle. Journal of Maxillofacial Surgery
1980;8:161-75.
BIBLIOGRAPHY
9. Nwoku AL. Rehabilitating children with temporo-
1. Abdel-Hakim AM. Stomatognathic dysfunction in mandibular joint ankylosis. International Journal of
the western desert of Egypt: an epidemiological Oral Surgery 1979;8:271-5.
survey. Journal of Oral Rehabilitation 1983;10:
461-8. 10. Pereira FJ Jr, Lundh H, Westesson PL. Age related
changes in retrodiscal tissue in the temporomandibular
joint. Journal of Oral and Maxillofacial Surgery 1996;54:
55-61.

11. Toller PA, Glynn LE. Degenerative disease of the
mandibular joint. In Scientific foundations of dentistry.
B Cohen, IRH Kramer (Eds). Heinemann, London
1976;605-19.

12. Widmaml SE, Westesson PL, Kim LK, Pereira FJ,
Lundh H, Tsaki MM. Temporomandibular joint
pathosis related to sex, age, and dentition in autopsy
material. Oral Surgery, Oral Medicine and Oral
Pathology 1994;78:416-25.

13. Yagi K, Abbas K. A study of ankylosis of the
temporomandibular joint in the Sudan. Report
Submitted to the Faculty of Medicine, University of
Khartoum, 1981.

PERNICIOUS ANEMIA • Neurological manifestations include tingling
sensations in the hands and feet, paresthesia
DEFINITION and numbness of the extremities due to
peripheral nerve degeneration.
Pernicious anemia refers to the anemia
• Stiffness, difficulty in movement, depression
characterized by impaired RBC maturation and irritability, etc. are also common.

secondary to insufficient vitamin B12 due to • Diminished vibratory and positional sense.
defective intrinsic factor required for its
ORAL MANIFESTATION
absorption through intestinal wall.
• Glossitis, glossodynia (painful tongue), loss of
Pernicious anemia is a type of chronic, taste sensation and glossopyrosis (itching and
burning tongue), etc. are the hallmark features
progressive, megaloblastic anemia of adults and of pernicious anemia.

is caused by deficiency of an intrinsic factor in • Tongue lesions may develop even before the
fall of blood hemoglobin level.
the stomach.
• The tongue often appears “beefy red” in color
Vitamin B12 and folic acid act as essential co- with areas of patchy ulcerations on the
factors for the maturation of RBC within the dorsum and lateral borders.

bone marrow. Although folic acid deficiency can • Sometimes, atrophy and inflammation of the
filiform papillae produces a “bald” appea-
be ameliorated by dietary supplements, the rance of the tongue and the condition is often
known as ‘Hunter’s glossitis’.
vpietranmiciinouBs12andeemficiiaebnycydiceatnanryotsubpeprleecmtiefnietds, in
as • Initially, the tongue is fissured or lobulated
and it eventually becomes smooth, flabby and
there is lack of a transport protein (intrinsic atrophic.

factor) in the intestine which is essential for its • Burning sensations may also develop in the
lips, buccal mucosa and other mucosal sites.
absorption.
• Few patients have inflammation and macular
CLINICAL FEATURES lesions in the entire oral mucosa, which cause
burning sensation, dysphagia and difficulty
There are four major cardinal features of in denture wearing.
pernicious anemia:
A. Abnormally large red blood cells. • Focal areas of atrophy, erythema and some-
B. Hypochlorhydria. times hyperpigmentation may occur in the
C. Neurologic and gastrointestinal symptoms. oral mucosa.
D. A fatal outcome, unless the patient receives
• There may be pallor in the oral mucosa with
lifelong injections of vitamin B12. purpuric spots and occasional aphthous-like
ulcerations.
CLINICAL PRESENTATION
• There is increased susceptibility to oral
• Generalized weakness, fatigue, palpitations, infections in pernicious anemia.
nausea, vomiting, anorexia, diarrhea, dyspnea,
headache, feeling of faint and weight loss,
etc.

• The above mentioned features develop due
to reduced oxygen carrying capacity of blood.

• Patients often have a smooth, dry and yellow
skin.

510 Essentials of Oral Pathology

HISTOPATHOLOGY CAUSES

• Histologically oral epithelial cells in pernicious • Inadequate absorption of iron in the body.
anemia reveal enlarged, hyperchromatic • Excessive loss of blood.
nuclei with prominent nucleoli and serrated • Increased demand for RBC.
nuclear membranes. • Decrease intake of iron in the body.

• Often there is marked atrophy of the epithe- CLINICAL MANIFESTATION
lium with loss of rete pegs and intra or subepi-
thelial chronic inflammatory cell infiltration. • Fatigue, easy tiring, lightheadedness and lack
of energy.
• Cellular atypia is sometimes present with
increased nuclear-cytoplasmic ratio and • Plapitations, dizziness and sensitivity to cold.
prominent nucleoli. • Lemon-tinted palor of the skin and genera-

DIAGNOSTIC ASSESSMENT lized weakness.
• Koilonychia (spoon-shaped finger nails) is an
• Total RBC count is reduced to less than
3 million per mm3 of blood, elevated mean cell important feature in iron deficiency anemia
volume (MCV) and mean cell hemoglobin and the patients often exhibit increased
concentration (MCHC). brittleness and cracking of the finger nails.
• Splitting of hair is also commonly seen.
• Decreased WBC count and mean cell
hemoglobin (MCH). ORAL MANIFESTATION

• If MCV is less than 96 fl (RBC is large), it • Pallor of the oral mucosa and gingiva with
frequently indicates pernicious anemia. atrophy and loss of keratinization (atrophic
mucositis).
• Peripheral blood smear shows oval, macro-
cytic and hyperchromic red blood cells. • In some patients, atrophic mucositis in the
aerodigestive tract or oropharynx may
• Bone marrow contains large number of predispose to the occurence of squamous cell
megaloblasts. carcinoma.

• Unconjugated bilirubin is elevated due to • Atrophic glossitis with patchy or diffuse loss
increased hemolysis. or flattening of tongue papillae and glosso-
dynia (painful tongue), etc.
• Serum lactate dehydrogenase (an enzyme
liberated from damaged tissue) level is • The tongue appears smooth, bald and red with
extremely high. a glazed appearance, it may be tendered and
have burning sensations (glossopyrosis).
• Schilling’s test detects the absence of intrinsic
factor in the stomach. • Dysphagia (difficulty in swallowing), recur-
rent aphthous ulcer and candidiasis of the oral
• Gastric secretion analysis reveals the presence mucosa.
of higher level of free hydrochloric acid.
• Abnormal bleeding from the ulcers, faulty
TREATMENT wound healing and angular cheilitis are
common.
Intramuscular injections of vit B12.
• Angular cheilitis is often caused by candida
IRON DEFICIENCY ANEMIA albicans and it presents reddening, cracking,
fissuring and discomfort in the angle of the
Iron deficiency anemia is a chronic, microcytic, mouth or commissural region.
hypochromic type of anemia, which occurs either
due to inadequate absorption or excessive loss • A manifestation of Iron deficiency anemia is
of iron from the body. Plummer-Vinson syndrome which presents
a triad of symptoms comprising of dysphagia,
It is the most common form of anemia and stomatitis (inflammation of the oral mucosa)
the erythrocytes besides being hypochromic and and atrophic glossitis.
microcytic, are also severely decreased in
number.

Oral Aspects of Hematological Disorders 511

• This syndrome primarily affects the middle- Decreased production of RBC is anemia,
aged woman and these patients are suscep- decreased production of WBC is leucopenia and
tible to oral cancers and pre-cancers. decreased production of platelets is thrombo-
cytopenia, whereas severe depletion of all cell
DIFFERENTIAL DIAGNOSIS types of blood is often known as pancytopenia
• Atrophic candidiasis which often develops in dysplastic anemia. In
• Hypothyroidism aplastic anemia, the bone marrow shows lack of
• Other anemias maturation of the hemopoietic stem cells.
• Chronic depression
• Allergic conditions. ETIOLOGY

DIAGNOSTIC ASSESSMENT The exact etiology of aplastic anemia is not
• Peripheral blood smear shows small (micro- known, probably it is an autoimmune disorder.
There are some other crucial factors which can
cytic) and pale (hypochromic) red blood trigger the disease:
cells. • Hereditary factor; e.g. Fanconi’s syndrome
• Hemoglobin level is decreased to as low as
3.6 g/100 ml. and dyskeratosis congenita.
• Total RBC count is dropped moderately but • Drugs and chemicals such as:
rarely it goes to below 3 million per mm3.
• Estimation of serum ferritin is also useful. – Chloramphenicol
• MCV, MCH and mean cell hemoglobin – Phenyl butazone
concentration (MCHC)—all are reduced. – Sulphonamides
• Serum iron level is decreased to 10 mg (normal – DDT, benzene, etc.
50–150 mg). • Radiation
• Hemosiderin is completely absent from the • Infections–tuberculosis, viral hepatitis
bone marrow. • Idiopathic.
• If GI tract bleeding is the suspected cause of
iron deficiency anemia, then the following CLINICAL MANIFESTATIONS
additional investigations are to be done.
– X-rays (GI tract series) The systemic and oral manifestations of Aplastic
– Stool examination for occult blood anemia are almost similar to leukemia (in terms
– Esophagoscopy, gastroscopy and sig- of anemic severity, bleeding tendency and
susceptibility to infections).
moidoscopy, etc. • It is more common in young adults and elderly

HISTOPATHOLOGY individuals.
Tongue shows atrophy of the covering epi- • Weakness, lightheadedness with dyspnea and
thelium with loss of papillae.
fatigue due to slight physical exertion.
Leukocytic infiltrations in the spinus cell layer • Marked pallor of the skin and petechiae.
as well as in the underlying connective tissue. • Frequent episodes of epistaxis and bruises.
• Numbness and tingling of the extremities.
TREATMENT • Generalized edema of the body and tachy-
300 mg ferrous sulfate tablet, 3 to 4 tablets per
day for 6 months. cardia.
• Fever and severe infections often occurs due
APLASTIC ANEMIA
to neutropenia.
Aplastic anemia is a rare life threatening hemor- • Severe and fatal hemorrhages.
rhagic disease characterized by general lack of
bone marrow activity, that results in decreased ORAL MANIFESTATIONS
formation of RBC, WBC and platelet cells.
• Petechiae, ecchymoses, purpuric spots and
frank hematoma formations in the oral cavity.

• Spontaneous gingival bleeding, occasional
uncontrolled hemorrhage and epistaxis, etc.
frequently occur due to platelet deficiency.

512 Essentials of Oral Pathology

• Extreme pallor of the oral mucous membrane. CAUSES
• Multiple areas of ulcerations in the oral
A. Hereditary causes
mucosa, gingiva and pharynx. Periphery of • Hereditary spherocytosis
the ulcer shows minimal erythema. • Glucose 6–phosphate dehydrogenase defi-
• Persistent oral infections including candi-
diasis. ciency (G6PD)
• Gingival hyperplasia is also sometimes • Sickle cell anemia
associated with aplastic anemia. • Thalassemia.
• Fulminating conditions like bacteremia and
septicemia, etc. may develop from simple oral B. Acquired causes
infections. I. Antibody- mediated haemolytic disorders:

HISTOPATHOLOGY • Acquired autoimmune hemolysis
• Paroxysmal cold haemoglobinuria
Histologically oral mucosa exhibits accumulation • Erythroblastosis fetalis.
of numerous microorganisms with extreme lack II. Haemolysis due to physical, chemical or biological
of inflammatory cell infiltration in the connective
tissue. agents:
• Physical agents: Hemolysis due to
DIAGNOSTIC ASSESSMENT
prolonged physical exercise
• RBC count is usually below 1 million/mm3. • Chemical agents: Chemical agents and
• WBC count may be as low as 2000/mm3.
• Platelet count may fall below 20000/mm3. drugs can cause damage to RBC cells to
• Bone marrow is fatty and contains only few produce anemia.

developing blood cells. Important chemical agents, which can
• Bleeding time prolonged but clotting time is cause hemolysis are–arsenic, lead, sulpho-
namides, potassium chlorate, methyldopa,
normal. naphthalene, mefanamic acid, etc.
• Biological agents: Several microorganisms
TREATMENT can cause hemolysis which include:

Blood transfusion, antibiotics, splenectomy and – Plasmodium falciparum
bone marrow transplant, etc. Approximately,
50 percent patients die within 6 months after – Clostridia
detection of the disease due to severe infections
and hemorrhage. – Streptococcus pyogenes.

HEMOLYTIC ANEMIA CLINICAL FEATURES

DEFINITION • Palor, weakness, lightheadedness and
fatiguability.
Anemia occurring due to increased hemolysis in
the body, which the bone marrow can not com- • Jaundice, recurrent infections, leg ulcers,
pensate even by increasing the production of etc.
RBCs.
• Dyspnea or other cardiovascular symptoms.
In case of recurrent hemolysis, a compensatory
erythroid hyperplasia of the bone marrow occurs, ORAL MANIFESTATIONS
which enhances the rate of erythropoiesis or the
production of RBC. However, when due to some • Palor or yellow tinge of the oral mucosa.
reason, the renewed rate of erythropoiesis is also • Discoloration of teeth in erythroblastosis
unable to compensate for the increased
hemolysis, anemia develops, which is termed as foetalis.
‘hemolytic anemia’. • Gingival hemorrhage.

DIAGNOSTIC ASSESSMENT

• Blood Hb percentage is often below to 10 gm/
dl.

• Erythrocyte survival rate about 12 days
(normal 120 days).

Oral Aspects of Hematological Disorders 513

• A fall in blood hemoglobin at the rate of 1 gm/ In thalassemia the RBC cells are functionally
ltr. per week should be regarded as a definite compromised and because of this more and more
indication of excess hemolysis. RBC cells are produced by the bone marrow to
meet the oxygenation demand, this often leads
• Reticulocyte count: Raised. to bone marrow hyperplasia.
• Unconjugated serum bilirubin: Raised.
• Fecal urobilinogen: Raised. CLINICAL MANIFESTATION
• Serum iron concentration: Raised.
• Coomb’s test: Negative. The disease is commonly detected in the first two
• Osmotic fragility of RBC cell: Decreased. years of life and siblings are commonly affected.
The thalassemia minor patients are generally
TREATMENT asymptomatic except the presence of persistent
anemia and occasional splenomegaly.
Treatment of anemia and effective management
of the underlying diseases. The features of thalassemia are as follows:
• Blood transfusion in severe cases. • The patients often suffer from jaundice with
• Steroids may be used in case of immune
yellowish palor of the skin.
mediated disorders. • Fever, chills, marked anemia (microcytic and
• Splenectomy should be done in case of
hypochromic), malaise, generalized weakness
spherocytosis. and lethargy, etc. are common.
• Administration of folic acid. • Hepatosplenomegaly is an important feature
of the disease, which often cause bulging of
THALASSEMIAS the abdomen.
• Bone marrow hyperplasia often produces
Thalassemias are a group of inherited, chronic, painless enlargement of mandible and
hemolytic disorder, which are characterized by maxilla, which often results in a typical
the production of extremely thin, fragile “chipmunk facies”.
erythrocytes called “target cells”. • Cholelithiasis and leg ulcers also develop
frequently.
These cells survive only few days in the peri- • Reduced oxygenation may lead to severe
pheral circulation as they are readily recognized infections in the tissue.
by the spleen and are destroyed. Destruction of • Most of the patients have a mongoloid facies
target cells often causes microcytic hypochromic with prominent forehead, depressed nasal
type of anemia in thalassemia patients. bridge, prominent cheek bones, protrusion of
the maxillary anterior teeth and slanting eyes,
In thalassemia, there is insufficient synthesis etc.
of α and β polypeptide chains of hemoglobin • In severe form of the disease, the onset is in
(these chains are otherwise completely normal). infancy and death often occurs in adolescence.
High output cardiac failure is the common
Either α or β chains can be affected by their cause of death in these patients.
diminished synthesis (inα -thalassemia— α-chain • Repeated blood transfusions may cause iron
synthesis slows down and in β-thalassemia— β- deposition in tissues (hemosiderosis), which
chain synthesis diminishes). As the β-thalassemia may lead to dysfunction of many glands and
is more common, it is called “classic or major other vital organs.
thalassemia” and its other name is “Cooley’s
anemia.” RADIOGRAPHIC APPEARANCE

Thalassemia is a autosomal recessive disease, • The skull bones radiographically exhibit thin,
the heterozygous form of the disease is mild poorly defined, inner and outer cortex of bone
which is known as thalassemia minor. The and the trabaculae between them are coarse,
homozygous form of the disease is very severe elongated and bristle-like, which produce a
and is known as thalassemia major. A third form typical “hair-on-end” or a “crew-cut”
of the disease is also recognized, which is called appearance on the surface of the skull.
thalassemia intermedia and is characterized by
clinical features which are of intermediate
severity between the major and the minor forms.

514 Essentials of Oral Pathology

Oral manifestations of thalassemia • Elevated HbA is found.
• Bone marrow is hyperplastic and produces
• Bimaxillary protrusion with painless enlargement
large numbers of immature, primitive looking,
of the jawbones. stem forms of RBCs.
• Excessive accumulations of alpha chains
• Spacing or flaring of anterior maxillary teeth. within the RBCs are called inclusion bodies
(Fessas bodies) and these bodies can be
• Pallor of the oral mucosa. detected by supravital staining (methyl violet)
of the peripheral blood.
• Xerostomia due to salivary gland dysfunctions
Key points of thalassemia
as a result of iron overload.
• Thalassemia is an inherited, chronic, hemolytic
• Severe malocclusion due to enlargement of the disorder characterized by the production of
extremely thin, fragile erythrocytes (target
jaws with marked open bite. cells).

• Prominent malar bones and mongoloid facies. • These cells survive only few days in the
peripheral circulation.
• Delayed pneumatization of maxillary sinuses.
• In thalassemia, there is insufficient synthesis of α
• Retracted upper lips. and β polypeptide chains of hemoglobin, if a
polypeptide chain synthesis is diminished, it is
• Discoloration of teeth due to iron deposition. called α- thalassemia and if β polypeptide chain
synthesis slows down it is called β -thalassemia.
• Zygomatic bones are pushed outwardly.
• As the β-thalassemia is more common, it is
• Depressed nasal bridge in severe cases. called “classic or major thalassemia” and its
other name is “Cooley’s anemia.”
• In the jaws, generalized rarefaction of the
alveolar bone, thinning of cortex and enlarged • Clinically patients have a mongoloid facies with
marrow spaces are found. prominent forehead, depressed nasal bridge,
prominent cheek bones and protrusion of the
• Radiograph of the ribs exhibit a typical ‘rib maxilla, etc.
within a rib’ appearance due to increased
radiodensity within or overlapping the • They suffer from severe anemia and frequent
medullary space of the ribs. jaundice with yellowish pallor of the skin,
hepatosplenomegaly, fever, weakness and
• Sometimes, the jaw bones show coarsening of lethargy, etc.
some bony trabaculae and blurring or dis-
appearance of others, it often produces a • Patients of thalassemia almost always have
typical radiographic appearance called “salt- bimaxillary protrusion with painless enlargement
and pepper effect”. of the jawbones, prominent malar bones,
spacing of anterior maxillary teeth, pallor of the
• Delayed pneumatization of the paranasal oral mucosa, xerostomia and severe malocclusion,
sinuses, especially the maxillary sinuses etc.

DIAGNOSTIC ASSESSMENT • Radiographically, the skull bone exhibits a typical
“hair-on-end” or a “crew-cut” appearance and
Laboratory findings in thalassemia include the jaw bones also exhibits a ‘salt and pepper’ effect.
following:
• Target cells (abnormally thin, fragile cells) and TREATMENT

other bizarrely shaped, nucleated RBC cells Multiple blood transfusions and splenectomy,
appear in the circulation. etc. Desferrioxamine, chelating agent may reduce
• The characteristic ‘safety-pin’ cells may be the effect of iron overload in tissues.
present in the circulating blood.
• WBC count may be raised up to 10,000 to
25,000 per cubic millimeter of blood.
• The serum billirubin and, fecal and urinary
urobillinogen are elevated because of severe
hemolysis.
• An elevated fetal hemoglobin is present.
• High percentage of HbF and HbA2 result from
the decrease in β-chains.

Oral Aspects of Hematological Disorders 515

SICKLE CELL ANEMIA • Asymptomatic pulpal necrosis, anesthesia and
paresthesia of the mandibular nerve.
DEFINITION
Sickle cell anemia is an inherited defect in the • Decreased bony density with coarse trabacular
synthesis of hemoglobin molecule, in which the pattern between root apex of tooth and the
erythrocytes assume a sickle or crescent shape. inferior border of mandible.
The defective erythrocytes are easily destroyed
causing severe anemia. • Extraction of tooth may lead to the develop-
ment of osteomyelitis especially in mandible.
PATHOGENESIS
Sickle cell anemia is an autosomal recessive type • Thrombosis of blood vessels and infraction in
of inherited disease, which is characterized by a the jawbone often produce ‘painful cries’.
point mutation in the Hb gene, which results in
an abnormal Hb molecule (HbS). Each person RADIOGRAPHIC FEATURES
inherits one gene from each parent, which
governs the synthesis of hemoglobin. HbS is less • Skull radiographs reveal multiple, small icicle
soluble than HbA (normal adult hemoglobin) like spicules across the calvarium, which
and the former forms long fibers, which deform produces a “hair-on-end” appearance.
the RBC into sickle shape. This crescent shaped
or sickle shaped RBC cells in sickle cell anemia • Occasionally infarcts develop in the
are more prone to agglutination. More agglutina- jawbones, which radiographically mimic
tions (hemolysis) of RBC leads to more anemia osteomyelitis. The bony infarcts are radio-
and increased viscosity of blood, moreover lucent in the beginning and later on they
increased risk of blocking of capillaries may become sclerotic.
result in ischemic damage in various organs and
the situation is known as ‘sickle cell crisis’. • Intraoral periapical radiographs reveal “step–
ladder” like trabeculae between contagious
CLINICAL FEATURES posterior teeth.
• Delayed physical growth and development of
• Increased osteoporosis and hyperplasia of the
the patient. bone marrow with thinning of individual
• Malaise, weakness and jaundice with a yellow cancellous trabaculae and cortex.

sclera. DIAGNOSTIC ASSESSMENT
• Pallor, loss of appetite, dehydration and
Sickle cells are viewed on a stained smear of
muscle rigidity. blood under microscope.
• Loss of consciousness is a common feature in
Total RBC count—Decreased.
severe cases (sickle cell crisis). Hb%—Lowered.
• Children do not develop any symptom until Hematocrit value—Decreased.
Serum unconjugated bilirubin—Raised.
late in the first year of life. Hb electrophoresis reveals the presence of
• Extreme susceptibility to infections, renal (Hb-S) in blood.

failure and CNS disturbances are common. TREATMENT
• There can be death due to wide spread
No specific treatment. Oxygen and blood trans-
ischemia, hypoxia and hypothermia. fusions in serious emergencies.
• Extreme pain in abdomen, lung, long bones
ERYTHROBLASTOSIS FETALIS
and joints due to ischemia and infarction.
• Fever, swelling of the joints, hands and feet, Erythroblastosis fetalis is a congenital hemolytic
anemia of newborn, which occurs due to the Rh
etc. are also common. incompatibility. The disease results from the
destruction of fetal RBC due to the reaction
ORAL MANIFESTATIONS between maternal and fetal blood factors.
• Oral mucosal polar can be seen and sometimes

the oral mucosa may be yellowish in color due
to hemolytic jaundice.

516 Essentials of Oral Pathology

PATHOGENESIS • A characteristic finding of the disease is the
“ruddy cyanosis” or a reddish-purple hue of
If the mother is Rh-negative, but the fetus is the face, extremities and lips due to the
Rh-positive, then the mother’s blood can develop presence of deoxygenated blood in the
antibodies (anti-Rh-agglutinins) against the Rh- cutaneous vessels.
factor of the fetus.
• Polycythemia vera may cause generalized
These antibodies may pass onto the fetus by pruritus (itching sensations) without any
crosing the placental and destroy its RBC cells, skin rash, moreover there may be burning
this often results in hemolysis, jaundice and sensations with erythema of the
anemia, etc. extremities.

ORAL MANIFESTATION • Hepatomegaly may occur as a late feature of
the disease.
• Black, brown or bluish discoloration of the
deciduous teeth in the child due to deposition ORAL MANIFESTATION
of blood pigments.
• Deep purplish red discoloration of the oral
• Enamel hypoplasia, which may produce a mucosa that is commonly reflected on the
“ring-like” defect on the tooth crowns and is tongue, gingiva, cheek and lip surfaces.
often termed as “Rh-hump”.
• The gingiva appears engorged and swollen,
POLYCYTHEMIA VERA and it bleeds profusely upon slight provo-
cation.
Polycythemia Vera is chronic disease charac-
terized by excessive proliferation of RBC cells, • Submucosal petechiae, hematoma and
usually with an increased Hb level and total ecchymoses, etc. are very common.
blood volume.
Key points of polycythemia vera
Secondary polycythemia: It is commonly
associated with hypoxia (cardiac or pulmonary • Polycythemia Vera is chronic disease charac-
disease), excessive production of erythropoietin,
steroid therapy or chronic exposure to chemicals, terized by excessive proliferation of RBC cells,
etc.
usually with an increased hemoglobin level and
CLINICAL FEATURES
total blood volume.
• The disease usually develops in middle age,
particularly among Jewish people. • The disease occurs more in middle aged males and

• Polycythemia Vera has a gradual onset and is patients often complain of dyspnea, headache,
more common in males.
dizziness, drowsiness and tinnitus, etc.
• Patient often complains of dyspnea, headache,
dizziness, drowsiness and tinnitus, etc • Often there is excessive sweating, weight loss,

• Often there is excessive sweating, weight loss, severe weakness, fatigue, impaired mental
fullness of head and face and pruritus, etc.
ability, slurring of speech and visual
• There is severe weakness, fatigue, impaired
mental ability and visual disturbances, etc. disturbances, etc.

• Patients often have slurring of speech, mental • A characteristic finding of the disease is the
confusion and are unable to concentrate.
“ruddy cyanosis” or a reddish-purple hue of the
• Patients may have a plethoric appearance and
they develop splenomegaly, coronary throm- face, extremities and lips due to the presence of
bosis and paresthesia of the cranial nerves, etc.
deoxygenated blood in the cutaneous vessels.
• Peptic ulcers, epigastric pain along with intes-
tinal, nasal or cerebral hemorrhages, etc. are • Oral manifestations of the disease include deep,
very common during the course of the disease.
purplish red discoloration of the oral mucosa

over the tongue, gingiva, cheek and lip surfaces.

• The gingiva appears engorged and swollen, and

it bleeds profusely upon slight provocation.

• Submucosal petechiae, hematoma and ecchy-

moses, etc. are also very common.

• Laboratory investigation reveals higher red blood

cell count, which may be as high as 8 to 12
million/mm3 of blood.

Oral Aspects of Hematological Disorders 517

• Often there is increased varicosity in the LEUKEMIAS
ventral surface of the tongue.
Leukemia is a malignant disease of the blood-
• Engorgement of all organs related with blood. forming organs, characterized by increased
proliferation of WBC cells in the bone marrow at
LABORATORY FINDINGS the cost of other hemopoietic cells. Although,
leukemia is a disease of the WBC cells, it often
• The red blood cell count may be as high as 8 severely affects the other major cell types of
to 12 million/mm3 of blood. blood, e. g. RBCs and Platelets, etc. The disease
produces anemia due to decreased production
• The bone marrow is hyperplastic with of RBC cells, there is increased susceptibility of
decreased marrow iron and it appears dark- infection due to production of immature and
red and highly cellular. functionally inefficient WBCs in large numbers
and there is also increased tendency for
• Striking increase in the total blood volume and hemorrhage due to reduced number of platelets
gradual increase in the blood viscosity. in the blood.

• Hemoglobin level may by 18 to 20 g/100 ml. INCIDENCE
• Hematocrit level is greater than 54 percent in
Leukemia accounts for 8 percent of all human
men and 49 percent in women. cancers and is the common malignancy in
• Platelet count is increased and often there is children and young adults. One-half of all
leukemias are classified as acute, with rapid onset
abnormal platelet aggregation. and progression of the disease resulting in 100
• Leukocytosis also common. percent mortality within days to months without
• Serum uric acid level is increased up to 3 to 4 appropriate therapy. The remaining leukemias
are classified as chronic, which have a more
times normal. indolent course.
• Increased granulocyte alkaline phosphatase
ETIOLOGY
activity.
Although, the exact cause of leukemia is
TREATMENT unknown, several predisposing factors have
been associated with this disease which include:
• Repeated phlebotomy (vene-section) may be • Chromosomal abnormality—the presence of
done to lower the Hb%, hematocrits and RBC
cell mass. an abnormal chromosome, e.g. Philadelphia
chromosome is associated with an increased
• 500 ml of blood is removed every 2 to 3 days incidence of chronic myelocytic leukemia
till the hematocrit reaches a desired level. (CML).
• Exposure to high doses of radiation therapy.
• Chemotherapy is given with chlorambucil, • Exposure to certain chemicals, e.g. benzene,
malphalan or cytosine arabinoside to reduce phenyl butazone and chloramphenicol, etc.
the number of RBCs. • Following chemotherapy treatment for some
other diseases, particularly with melphalan.
• There is an increased chance of thrombosis, if • Myeloproliferative disorders like-polycy-
the patients are on bed rest and therefore themia vera, etc.
patients should be kept ambulatory. • Congenital or genetic abnormalities (e.g.
Down’s syndrome).
COMPLICATIONS OF POLYCYTHEMIA VERA • Presence of primary immune deficiency.
• Infection with human leukocyte virus (HTLV-
• Thrombophlebitis, myocardial and cerebral 1—human T-cell Leukemia virus-1).
infarctions.

• Thrombotic occlusion of the splenic, hepatic,
portal and mesenteric veins.

• Hemorrhage— nasal, intestinal and cerebral,
etc.

• Digital gangrene and necrosis.
• Gout–Due to over production of uric acid.
• Congestive cardiac failure due to increased

blood volume and hypertension.
• Acute leukemia may be a terminal compli-

cation of polycythemia vera.

518 Essentials of Oral Pathology

• Hereditary—Some families have increased A. Chronic myelogenous leukemia (CML).

incidences of leukemia than others. B. Chronic lymphocytic leukemia (CLL).

CLASSIFICATION OF LEUKEMIAS CLINICAL FEATURES OF LEUKEMIAS

Leukemias are broadly classified into acute and • Acute leukemias occur commonly either in
chronic types. children aged between 2 and 4 years and in
adult patients aged 65 years or above. Chronic
Acute Leukemia leukemias on the other hand occur in patients
between the ages of 25 and 60 years.
It is characterized by neoplastic proliferation of
large number of abnormal, immature leukocytes • Both types of leukemia occur predominantly
in the marrow that infiltrate the lymph nodes, among males.
liver, spleen and eventually all body systems.
• Patients often complain of fatigue, generalized
In addition to this, production of other blood malaise and weakness.
cells (i.e. red blood cells and platelets) are
inhibited, which results in inadequate oxygen • Easy bruising, epistaxis, headache, vomiting
transport, thrombocytopenia and immune and generalized pain, etc.
system malfunction, etc.
• Most of the patients may have the feeling of ab-
According to the French-American-British dominal fullness due to hepatosplenomegaly.
(FAB) cooperative group, the acute leukemias are
classified in the following manner: • Decreased production of RBC causes anemia
and severe pallor.
Chronic Leukemias
• Persistent fever of unknown etiology due to
These diseases have a gradual onset and a more depressed immunity.
protected course than the acute forms. The white
blood cells produced are more mature and thus • Weight loss and heat intolerance due to
can better defend the body against invading increased rate of body metabolism.
microorganisms.
• Pain from infarction of the spleen.
Chronic leukemias are again classified into • Scattered petechiae, ecchymosis over the skin
two types:
and generalized lymphadenopathy.
• Generalized bone and joint pain, shortness of

breath, tachycardia and dyspnea on slight
exertion, etc. are the other common features
of the disease.

Acute Leukemia Classification of leukemias
Chronic Leukemia

Acute Lymphocytic Leukemia (ALL) Chronic myelogenous leukemia (CML)
L1—Common childhood leukemia.
L2—Adult ALL.
L3—Rare subtype, blast cells

resemble Burkitt’s lymphoma.

Acute Myeloblastic Leukemia (AML) Chronic lymphocytic leukemia (CLL)
Granulocytic
M1—Myeloblastic leukemia without maturation.
M2—Myeloblastic leukemia with maturation
M3—Hypergranular promyelocytic leukemia
Monocytic
M4—Myelomonocytic leukemia
M5—Monocytic leukemia
Erythroid
M6—Erythroleukemia

Oral Aspects of Hematological Disorders 519

Oral manifestations of leukemia

Oral manifestations in leukemia may be caused by the basic disease process itself or the secondary
infections or due to local irritations aggregated by plaque, food debris and ill fitting dentures, etc.

• Gingival hyperplasia with severe bleeding tendency is the most common oral manifestation of leukemia.
• Diffuse hyperplastic gingivitis with cyanotic bluish discoloration of the gingiva. Moreover the gingivitis

is often associated with mucositis.
• The gingival tissue becomes swollen and edematous due to leukemic cell infiltration and the overgrowth

of gingival tissue may cover the entire teeth of the dental arch (Figs 17.1 and 17.2).
• There can be marked enlargement of the interdental papillae and sometimes boggy, non-tendered,

tumor-like swellings (often called leukemic cell deposits) may also be seen in the gingiva palate and
salivary glands, etc.
• Thinning of the oral mucosa and bone marrow depression can allow increased opportunistic infections
in the mouth.
• Bacterial infections in the oral cavity often lead to septicemia.
• Infiltration of leukemic cells into the periapical region of tooth often simulates conventional periapical
lesions.
• Leukemic cells can infiltrate into the extraction sockets and cause delayed healing with severe bleeding
and secondary infections.
• Blockade of the bone marrow vessels and secondary infections often lead to the development of
osteomyelitis in the jaw after tooth extraction.
• Besides this, ulceration of the sulcular epithelium and necrosis of the connective tissue leads to severe,
spontaneous gingival bleeding.
• Petechiae, mucosal pallor, ecchymosis, hemorrhage and hematoma formations in the oral mucosa are
common (Fig. 17.3).
• Multiple large irregular necrotic ulcers develop in the oral mucosa due to secondary infection by various
organisms, the ulcers are usually surrounded by a pale zone and these lesions produce excessive foul
smell (Fig. 17.4).
• Large hematomas often develop on the lower lip.
• Oral infections, e.g. candidiasis, histoplasmosis, aspergillosis and HSV infections are common in leukemic
patients due to the absence of mature, healthy WBC cells and these secondary infections may produce
fatal complications.
• Palatal ulcerations and necrosis may herald the presence of mucormycosis of the nasal cavity and the
paranasal sinuses.
• Deep, punched-out ulcers with grayish-white necrotic base may occur due to extreme neutropenia.
• Rapid loosening and spontaneous exfoliations of teeth due to necrosis of the periodontal ligament and
destruction of the alveolar bone.
• Mental nerve neuropathy or the ‘numb chin syndrome’ is a constant finding in leukemia.
• Leukemic cell infiltration in the dental pulp may sometimes cause atypical dental pain.
• Prolonged post-extraction bleeding can be a serious problem in acute leukemia.

• Hyperuricemia with renal pain and retinal DIAGNOSTIC ASSESSMENT

hemorrhages. A comprehensive evaluation of all body systems
• Severe infections like pneumonia and septice- is necessary for establishing the diagnosis and
treatment plan for leukemia.
mia, etc. may develop in cases of severe
leukemia. CBC VALUES (COMPLETE BLOOD COUNT)

• Cerebral hemorrhage, increased intracranial Peripheral Blood Picture:
pressure and cranial nerve palsies. • WBC total count may be either normal, or

• Leukemic cell infiltrations into the skin, abnormally low (less than 100/mm3) or
mucosa and retina, etc.

520 Essentials of Oral Pathology

Fig. 17.1: Gingival swelling in a patient Fig. 17.4: Necrotic ulcerations of oral mucosa
with acute myeloid leukemia in the patient with acute myeloid leukemia

Fig. 17.2: Severe gingival swelling in the Key points of leukemia
patient with acute myeloid leukemia
• Leukemia is a malignant disease of the blood-
Fig. 17.3: Areas of ecchymosis of skin (extensor forming organs, characterized by increased
surface of hand) in the same patient proliferation of WBC cells in the bone marrow
at the cost of other hemopoietic cells.

• Leukemias are broadly divided into two groups—
acute and chronic. Acute leukemias occur
commonly in children while chronic leukemias
are seen more commonly in middle aged adults
and older people.

• Patients often complain of fatigue, weakness,
easy bruising, epistaxis, ecchymoses, headache,
vomiting and generalized weakness, etc.

• The other important features of the disease
include hepatosplenomegaly, severe pallor and
lymphadenopathy, etc.

• Oral manifestations of the disease include gin-
gival hyperplasia with severe bleeding tendency.

• There is also presence of diffuse hyperplastic
gingivitis with cyanotic bluish discoloration of the
gingiva. Moreover the gingivitis is often
associated with mucositis.

• The gingival tissue presents areas of tumor-like
swellings, which occur due to deposition of
leukemic cells within the tissue.

• Blood report shows total WBC has become
abnormally high (more than 20,00,000/mm3)
with abnormal marrow activity.

extremely high (greater than 20,00,000/mm3).
Generally the WBC count of the peripheral
blood ranges from 10,000 to 100,000 per 1 ml
of blood.
• Differential count of WBC may reveal that
one type of leukocyte is overwhelmingly
predominant.

Oral Aspects of Hematological Disorders 521

• There may be abnormal leukocytes, including • Toxic effects of some drugs, e.g. sulfonamides,
immature blast forms in the peripheral blood. chloramphenicol, anti-histaminics and
chlorambucil, etc.
• The platelet count and hemoglobin levels are
usually low. • Due to the hypersensitivity to drugs like
aminopyrine.
Bone marrow aspiration: Biopsy or bone marrow
aspiration reveals an overall increase in the • Long-term administration of analgesics
number of bone marrow cells, with an increase (phenyl butazone), antithyriods, diuretics,
in the proportion of leukocyte series. cytotoxic drugs and anticoagulants, etc.

Lumbar puncture: It determines the presence of • Ionizing radiation, tuberculosis, typhoid fever
blast cells in the central nervous system. and malaria, etc. may also induce agranulo-
cytosis.
Radiographic test: Radiographic tests may
include the following: CLINICAL FEATURES
• Chest X-ray—To detect the mediastinal
• The disease starts with high fever, chills and
involvement. sore throat, etc.
• Skeletal X-ray—To detect skeletal lesions.
• MRI and CT Scans—To detect lesions and • Patients gradually develop malaise, weakness,
bone pain and increased prostrations.
sites of infection, especially in the head and
neck areas. • The skin appears pale and in many cases there
may be sings of jaundice.
Lymphangiogram: Lymphnode biopsy or
lymphangiogram may be performed to locate • Persistent bacterial infections develop in many
malignant lesions and accurately classify the parts of the body with regional lymphadenitis.
diseases.
• Severe dysphagia, weak and rapid pulse, etc.
TREATMENT are the other important features of the disease.

Antileukemic chemotherapy and radiotherapy. • Urinary tract infections with vaginal and rectal
Repeated blood transfusions and administration ulcerations are common.
of antibiotics.
• Without prompt antibiotic therapy the disease
AGRANULOCYTOSIS usually causes death within a week due to
(GRANULOCYTOPENIA) pneumonia, sepsis and shock, etc.

Agranulocytosis is a serious acute leukopenia, Oral manifestations of agranulocytosis
characterized by a significant decrease in the
number of granular leukocytes (chiefly the • Agranulocytosis causes narcotizing ulcerations
neutrophils).
called ‘agranulocytic angina’ of the oral mucosa
ETIOLOGY
that involve the gingiva, soft palate, tonsils, lips,
The disease commonly occurs among adult
females and interestingly it frequently affects the pharynx and cheek, etc.
health professionals.
• These ulcers are deep and are covered by a
The exact etiology of agranulocytosis is not
known, however, investigators believe that the yellow or grey membrane, but there is absence
disease may occur due to certain drugs and
chemicals, which suppress the bone marrow. The of any red halo due to the lack of inflammation.
agents and their effects are as follows:
• Gingival bleeding, excessive salivations and

dysphagia, etc. are also common.

• Halitosis and hemorrhagic ulcers are often

present and the patients feel extreme difficulty

in taking food.

• Excessive tendency for developing secondary

infections, which develop rapidly and soon

become overwhelming. These lesions often

resemble acute necrotizing ulcerative gingivitis

(ANUG).

• Opportunistic fungal infections are also common.

522 Essentials of Oral Pathology

HISTOPATHOLOGY upper respiratory tract infections in uniformly
spaced episodes.
Biopsy taken from the oral ulcer reveals nume- • Patients develop short term fever on regular
rous bacterial organisms both on the surface and basis along with anorexia, malaise and
deep inside the tissue. Inflammatory response in lymphadenopathy, etc. which spontaneously
the tissue is very little. resolve once the neutrophil count returns to
normal.
DIAGNOSTIC ASSESSMENT • Aphthous-like ulceration in the month of short
duration develop upon minor trauma, the
Diagnosis of arganulocytosis is made on the basis areas commonly affected are lips, tongue,
of the following: buccal mucosa and oropharynx, etc.
• WBC count reveals severe leukopenia (500 to • Oral ulcers often have an erythematous ‘halo’
at the periphery.
3000/mm3) with extreme reduction in • Cyclic neutropenia also characteristically
neutrophil count (0 to 2%). produces rapidly progressive periodontal
• Bone marrow examination reveals an absence disease at an early age, which presents severe
of granulocytes, a maturational arrest of gingival recessions, rapid alveolar bone loss
young developing cells or an increased and tooth mobility, etc.
number of myeloid precursors (signifying
peripheral granulocyte destruction). DIAGNOSTIC ASSESSMENT
• Cultures of urine, blood and materials taken
from lesions in the throat and mouth, etc. are • Total WBC count decreases to 3000 cells/cu
positive for bacteria (usually gram-positive mm of blood in every month.
cocci).
• A history of exposure to an offending agent, • The neutrophil count falls below a critical level
plus all the above findings (especially in case of 500/cumm for 3 to 5 days and then it rises,
of a person, who medicates himself or herself) the same cycle repeats in about every 3 weeks.
are generally diagnostic for agranulocytosis.
• Blood monocyte and eosinophil count
TREATMENT increases as the neutrophil count falls.

Elimination of causative factors, antibiotics, • In cyclic neutropenia, the neutrophil count is
vitamins, antipyretics and high caloric soft always far below normal even during the
diet. remission period also.

CYCLIC NEUTROPENIA • Oral ulcer histologically shows absence of
infiltrating neutrophils.
DEFINITION
TREATMENT
Cyclic neutropenia is an idiopathic disease
characterized by episodic defects in neutrophil No specific treatment.
maturation in the bone marrow, resulting in
periodic fall in circulating neutrophils at regular PURPURA
intervals of 3 to 4 weeks. The condition is episodic
in nature and is characterized by severe Purpura is defined as the extra-vasation of small
infections as the neutrophil count falls below amount of blood into the skin or mucous
the critical level, moreover the symptoms subside membrane, causing petechiae, ecchymosis or
as the neutrophil count rises towards normal. spontaneous bruising, etc. The disease purpura
results from platelet disorder or occasionally due
CLINICAL FEATURES to vascular defects and is characterized by
prolonged bleeding time (BT) but normal clotting
• Cyclic neutropenia generally affects children functions.
and the patients often suffer from recurrent

Oral Aspects of Hematological Disorders 523

Drugs which may cause purpura

• Chloramphenicol
• Phenylbutazone
• Indomethacin
• Thiazide
• Diuretics
• Quinine
• Quinidine.

TYPES Fig. 17.5: Multiple petechial spots on the skin of a patient
with thrombocytopenic purpura
The disease is of two types:
A. Idiopathic thrombocytopenic purpura (ITP)
B. Non-thrombocytopenic purpura

ITP refers to thrombocytopenia caused by
an unknown, possibly autoimmune disease.
This disorder is characterized by premature
destruction of platelets due to the formation of
antibodies against them. The platelets are then
destroyed by phagocytosis in the spleen or in the
liver.

Normally, platelet cells survive 8 to 10 days
within the circulation but in ITP the platelet
survival time is as brief as 1 to 3 days or less.

Non-thrombocytopenic purpura occurs due to
the rupture of smaller blood vessels with
resultant bleeding into the tissue.

Major forms of this disease are:
• Familial hemorrhagic telangiectasia
• Anaphylactoid purpura
• Toxic purpura.

CLINICAL FEATURES OF PURPURA Fig. 17.6: Spontaneous bleeding from gingiva and buccal
mucosa in the patient with purpura
• Purpura commonly occurs among adults
below 40 years of age and females are more • Localized oral purpura is a condition charac-
frequently affected than males. terized by development of blood blisters on
the oral mucosa due to minor trauma.
• The disease is characterized by sudden,
spontaneous occurrences of petechiae (Fig. • In purpura, the bleeding spots on the skin or
17.5) (small pinpoint hemorrhage under the skin mucosal surfaces do not blanch upon pressure.
or mucosa), ecchymosis (escape of blood into
tissues producing a large bruise) or hematomas • Excessive bruising tendency, epistaxis,
(blood filled tumors) in the skin and mucous hematuria, melena and hematemesis are
membrane. common.

• Purpuric spots are often seen on the palate,
where the posterior border of artificial denture
presses against the palatal mucosa.

• Excessive gingival bleeding and blood blisters
in the oral mucosa, the blisters often rupture
and leave ulcers (Fig. 17.6).

524 Essentials of Oral Pathology

• Spontaneous bleeding often does not occur DIAGNOSTIC ASSESSMENT
unless the platelet count is below 20,000 per
cu mm of blood. • Platelet count below 100,000/mm³ of blood
(normal platelet count is 2.5 to 4 lac/cumm of
• Women may have extremely heavy menses blood).
or bleeding between periods.
• Spontaneous bleeding occurs if the platelet
• The disease causes prolonged bleeding after count goes below 20000/mm³.
surgery or injury.
• Prolonged bleeding time with normal
• Bleeding into the diaphragm may result in coagulation time.
pulmonary complications.
• Increased capillary fragility as demonstrated
• Intracranial hemorrhage may produce pares- by ‘tourniquet test’.
thesia of the cranial nerves and hemiplegia.
• Positive platelet antibody screening.
• Bleeding into the muscles and joints may cause • Bone marrow aspirates contain normal or
difficulty in movements.
increased number of megakaryocytes.
• Prolonged oozing of blood from different sites • Examination of urine reveals proteinuria or
may occur in severe cases, despite local
measures to curtail bleeding. hematuria.
• Gingival tissue biopsy with PAS stain reveals
• Interestingly, the spleen is not palpable and if
it is palpable, leukemia should be suspected fibrin deposits within the small capillaries.
rather than purpura.
Key points of purpura
Oral manifestations of purpura
• Purpura is the extravasation of small amount of
• Profuse gingival bleeding and development of blood into the skin or mucous membrane;
blood blisters, which occurs either sponta- causing petechiae, ecchymosis or spontaneous
neously or upon slight provocation. bruising, etc.

• Bleeding starts typically after a short delay • It results from decreased platelet count or
following injury as platelets and vascular occasionally due to vascular defects and is
response provide initial phase of hemostasis. characterized by prolonged bleeding time (BT)
but normal clotting time (CT).
• Persistent uncontrolled hemorrhage may
continue for days and untreated patients often • Purpura is of two types—Idiopathic thrombocy-
topenic purpura (ITP) and non-thrombocyto-
die. penic purpura.

• Petechiae or ecchymosis occurs very frequently • Clinically, the disease presents sudden, spon-
on the palatal mucosa (where posterior border taneous occurrences of petechiae, ecchymosis
of the denture presses into the palatal mucosa), and hematomas over the skin and mucous
however other intraoral structures may also be membrane.
involved.
• Oral manifestations of the disease include
• Excessive uncontrolled bleeding occurs following purpuric spots on the oral mucosa (especially
minor surgical procedures including dental palate), excessive gingival bleeding and blood
extractions (however unlike hemophilia, bleed- blisters in the oral mucosa.
ing in purpura ultimately stops spontaneously
as a result of normal coagulation of blood). • Excessive bruising tendency, epistaxis,
hematuria, melena and hematemesis are
• Submucosal hematomas often develop in the common.

oral cavity following trauma, and these lesions • Blood report reveals platelet count below
appear as large, dark tumors. 100,000/mm³ of blood.

• Bleeding into the facial muscles may cause • Spontaneous bleeding occurs if the platelet
difficulty in opening and closing the mouth. count goes below 20000/mm³ of blood.

• Bleeding into the temporomandibular joint
results in pain and trismus.

Oral Aspects of Hematological Disorders 525

TREATMENT • Interestingly, no petechial spots are found on
the skin or mucosal surfaces.
By steroid therapy and repeated blood trans-
fusions. Splenectomy and immunosuppressive • Severe fatal epistaxis after injury to the nose.
drug therapy may be required. • Gastric hemorrhage may occur in case a

HEMOPHILIA gastric ulcer is present.
• Recurrent hemarthrosis (bleeding into the
Hemophilia is a potentially fatal inherited
bleeding disorder characterized by profound joints) occurs commonly in elbow, knee and
hemorrhage due to the genetic deficiency of ankle joints, etc. and untreated or recurrent
clotting factors. The disease occurs in males but cases may result serious joint deformity and
is transmitted by females and the incidence rate permanent crippling.
is 1 in 8,000 to 10,000 populations. • Joint problems mostly occur due to degene-
rative changes in the joint structures,
ETIOLOGY osteoporosis and muscle atrophy, etc.
• Patients often have spontaneous hematuria
• Heredity and intracranial hemorrhage.
• Sex-linked recessive trait
• Spontaneous mutations may sometimes cause Oral manifestation of hemophilia

the condition (when the family history is • Severe hemorrhage from the gingival tissue after
negative for the disease).
surgical incision, curettage or dental extraction.
TYPES
• Bleeding may even start after brushing the teeth
There are three major types of hemophilia.
A. Hemophilia A (classic hemophilia) with a hard toothbrush.
B. Hemophilia B (Christmas disease)
C. Von Willebrand’s disease • Following the surgical or traumatic injury

Since, the classic hemophilia constitutes about bleeding starts after a short delay as the normal
80 percent of all hemophilias, the discussion on
clinical features and treatments, etc. will be made platelet or vascular responses provide initial
mostly in reference to this entity.
phase of hemostasis. Severe bleeding however
CLINICAL FEATURES OF HEMOPHILIA
starts after this, which if not controlled may
• The disease is seldom diagnosed in infancy
unless serious bleeding occurs from the continue for weeks or until the patient dies.
umbilical cord or following circumcision.
• Slight trauma (e. g. common bumps or fall in
• It is usually diagnosed after the child becomes
active. small babies) may lead to ecchymosis or

• The disease is mostly characterized by easy hematoma formations in the tongue, lips or
bruising and prolonged bleeding, particularly
after minor accidental, surgical or dental palate, etc.
trauma.
• Severe bleeding unexpectedly occurs from the
• Bleeding into muscles and joints in affected
children cause pain, swelling and difficulty in tiny injection sites in the mouth.
movement of the affected organ.
• Internal bleeding into the glottis with
• Spontaneous bleeding into the subcutaneous
tissue or internal organs leads to recurrent soft subsequent air-way obstruction may occur
tissue hematoma formation.
following pterygomandibular-block-anesthesia,

which may cause death of the patient.

• Recurrent subperiosteal hematoma with reactive

new bone formation may cause tumor-like

malformations of the jaw (such lesions are called

pseudo-tumor of hemophilia).

• Hemophilic patients often carry a high caries

index and severe periodontal disease.

• Deep tissue bleeding in oropharyngeal region is

often a feared complication of hemophilia as it

can obstruct the airway and therefore require

emergency intubations.

526 Essentials of Oral Pathology

• In cases of mild hemophilia, no major bleeding • Prophylactic transfusion of factor VIII to a
symptoms are present unless there is an injury level of 50 percent above normal is
or any surgical intervention carried out in the recommended in cases of minor injury or
patient. dental extractions.

LABORATORY INVESTIGATIONS • Topical bleeding can be temporarily controlled
by applying pressure to the injured site or
• Clotting time is prolonged or sometimes it packing the area with fibrin foam, and by
may test normal. applying topical hemostatic agents such as
thrombin.
• Platelet count and bleeding time is normal.
• Prothrombin time is normal. • Analgesics and corticosteroids reduce joint
• Prothrombin consumption—Decreased. pain and swelling.
• Activated partial thromboplastin time is
• Joint immobilization and local chilling
prolonged. (packing ice around the joint) may give relief
• Thromboplastin generation—Increased. in case of hemarthrosis. If the pain is severe it
• Genetic counseling and carrier detection by may be necessary to aspirate blood from the
joint.
biologic and immunologic assays.
• Blood grouping and cross matching. • In mild hemophilia, the use of intravenous
• Specific quantitative assays for factor VIII will desmopressin (acts by increasing factor VIII
activity) may eliminate the need of AHG.
determine the severity of the disease.
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