Malignant connective tissue tumors

Cleidocranial dysplasia

Etiology

a rare congenital disorder of bone with

an autosomal dominant hereditary

mode of inheritance with complete

penetrance, but variable expressivity

caused by mutation in the CBFA1gene

mapped on chromosome 6p21

encoding transcription factor RUNX2

responsible for osteoblast

differentiation

Clinical features

Moderately short stature, and

They tend to have a short head from

front to back (brachycephaly) and

a prominent forehead (frontal bossing).

delayed closure of fontanels, and some

adults with CCD have open fontanels.

The eyes are widely spaced, and

the nasal bridge is often flat.

one or both clavicles are frequently

partially or in 10% cases completely

absent.

The neck appears long, and the

shoulders are narrow and down-

sloping

hypermobility of shoulders with

tendency to approximate shoulders

anteriorly

Oral manifestations

prolonged retention of deciduous

dentition and delayed eruption of

permanent teeth.

Adults have mixed dentition in their

oral cavities.

show a large number of unerupted

supernumerary teeth, often mimicking

a premolar.

Delayed and imperfect ossification of

the cranium,

Maxilla is also underdeveloped along

with ill-formed paranasal sinuses.

Skeletal Class III tendency /

mandibular prognathism in CCD->

uninterfered growth due to hypoplastic

maxilla and upward and forward

mandibular rotation.

Treatment

No specific treatment suggested

Cherubism

Etiology

SH3-binding protein SH3BP2 mapped

to 4p16.3, an important molecule in

cell signaling

There is bone loss followed by the

accumulation of fibrous tissue that

causes facial swelling especially

around the cheeks, hence the

disease's name.

Clinical features

Age: in children

Sex: M=F

Site: Mand>max

severe bone degradation of both the

upper and lower jaws beginning at

about age three.

In adult life, complete involution of the

lesions

In some cases, the enlargement of the

floor of the orbit (the bones

surrounding the eye socket) causes

the eyeball to tip upward.

The name derived from cherub

(angelic looking, as depicted in

Renaissance paintings)

Oral manifestations

Abnormal patterns of teeth eruption

teeth agenesis and the presence of

ectopic or retained teeth.

X-ray

multilocular radiolucencies->near the

angle of the mandible and spreading

to the mandibular ramus and body.

HP

The histology is limited for diagnosis, showing fibrous hyperplasia and multinucleated giant cells.

similar to those other bone diseases such as

brown tumor of hyperparathyroidism,

giant cell tumor, and

central and peripheral giant cell granuloma

Lab diagnosis

the bone markers

phosphorous,

serum calcium, and

alkaline phosphatase are usually

at normal levels with respect to age.

cherubism may be associated with

other genetic diseases, such as

Noonan’s syndrome and Ramon

syndrome.

Treatment

multinucleated cells in cherubic

lesions ->osteoclasts from a structural

and biochemical standpoint so

calcitonin is the treatment of choice.

Pagets disease of bone

Pathogenesis

Paget disease occurs when there is a disturbance in the bone remodeling

that characteristically begins with unwarranted bone resorption followed by an increase in bone formation.

This osteoclastic hyper activity followed by substituted osteoblastic activity leads to the formation of a structurally disordered mosaic of bone which is still a woven bone,

and which is mechanically larger, weaker, more vascular, less compact, and more prone to fracture than normal adult lamellar bone

Slow virus:

paramyxovirus

respiratory synctial virus

Sequestrome 1 gene on chromosome

5.

Clinical features

Age: occurs in the aging skeleton

Sex:M=F

Site skull, spine, pelvis, and long

bones of the lower extremity.

Presentation

The bone pain is dull, constant,

boring, and deep below the soft

tissues.

It may persist or exacerbate during the

night.

Pathologic fractures commonly result

from weakened pagetic bone.

Nonspecific headaches,

impaired hearing, and tinnitus commonly result from skull involvement and compression of the 8th cranial nerve

The patient's hat size may increase (or, less commonly, decrease) as a result of skull enlargement or deformity.

These may manifest as nausea, dizziness, syncope, ataxia, incontinence, gait disturbances, or dementia.

3 phases:

Lytic

Mixed

Sclerotic

Oral manifestations

Facial disfigurement and

malocclusion may be observed

following enlargement of the maxilla or

mandible.

Tooth loss may occur with progressive

root resorption.

X-Ray

Absent periodontal membranes and

lamina dura are associated with

hypercementosis.

Both osteolysis (seen as radiolucency) and excessive bone formation(radiopacity) and a mixed state occurs.

There are specific X-ray features of Paget's disease that include:◦ A classical V-shaped pattern between healthy

and diseased long bones known as 'the blade of grass' lesion.

◦ The 'cotton wool' pattern in the skull that is also characteristic (multifocal sclerotic patches).-osteitis circumscripta

HP

woven bone and irregular broad trabeculae with disorganized cement lines in a mosaic pattern. Woven bone seperated by reversal lines

fibrous vascular tissue interspersed between trabeculae

profound bone resorption - numerous large osteoclasts with multiple nuclei per cell◦ virus-like inclusion bodies in osteoclasts

◦ Paget's osteoclasts larger, more nuclei than typical osteoclasts

Multinucleated giant cells-3-30 as opposed to 1-3 in normal osteoclasts

Treatment

NSAIDs

Bisphophonates

Calcitonin

Surgery

Lab investigations

Bone-specific alkaline phosphatase

(BSAP) levels are raised.

Urine hydroxyproline ↑.

Serum calcium, phosphorus, and

parathyroid hormone levels are

usually normal but immobilization may

lead to hypercalcaemia.