Malignant

Tumors of bones

Done by :

عبدالجليل خالد محمد عبدالستار

• Supervised by :

Dr : Ghazi AL-Ariki

الجمهورية اليمنية وزارة التعليم العالي

جامعة تعز كلية الطب و العلوم الصحية

قسم العظام–طب بشري

Malignant bone tumors

OUTLINE Introduction

What is a bone tumor ?

Epidemiology ( Incidence )

Causes & Risk factors .

Classification of Bone tumors

Diagnosis of bone tumors

Staging of Bone tumors

Malignant Bone Tumors

Introdution

Bones are classified according to their

shape-

Long bone

Flat bone

Short bone.

Long bone anatomy•Long bone consists of :

–Diaphysis: long shaft of bone–Epiphysis: ends of bone

–Epiphyseal plate: growth plate–Metaphysis: b/w epiphysis and diaphysis

–Articular cartilage: covers epiphysis–Periosteum: bone covering (pain sensitive)–Sharpey’s fibers: periosteum attaches to

underlying bone–Medullary cavity: Hollow chamber in bone

- red marrow produces blood cells- yellow marrow is adipose.

–Endosteum: thin layer lining the medullary cavity

Intro. Histology of bone tissue

Cells are surrounded by matrix.- 25% water- 25% protein- 50% mineral salts

4 cell types make up osseous tissue- Osteoprogenitor cells- Osteoblasts (bone forming cells )- Osteocytes- Osteoclasts (bone resorbing cells )

Intro. Histology of bone tissue

Osteoprogeniter cells &Osteoblast

Osteoclast

Introduction A tumor : is a lump or mass of tissue that forms when cells

divide uncontrollably. A growing tumor may replace healthy

tissue with abnormal tissue .

A bone tumor, is a neoplastic growth of tissue in bone.

Abnormal growths found in the bone can be either benign

or malignant.

It may weaken the bone, causing it to break (fracture).

Most bone tumors are noncancerous (benign). Some are

cancerous (malignant).

Benign tumors are usually not life-threatening.

Malignant tumors can spread cancer cells throughout the body (metastasize). This happens via the blood or lymphatic

system

By far the commonest malignant lesions in bones

are metastatic tumors which are not strictly speaking

‘bone, tumors, i.e. not of mesenchymal origin .

Intro.• Bone tumors are very diverse in morphology and

biological potential (can be no big deal or rapidly fatal) .

• Most benign lesions are seen <30 years of age• A new bone tumor in the elderly is more likely to be

malignant• No bone is safe (though most primaries are in long

bones)• Locale in the bone gives important Dx info• More common benign lesions typically present as

incidental findings (non-painful, stable size)• Be cautious with painful lesions and those that grow

relatively fast (over weeks or months)• Pathological fracture can be the first sign of tumor

Epidemiology & incidince

Primary bone tumors are relatively uncommon .

the incidence of benign bone tumors is higher than

the incidence of primary malignant tumors .

bone sarcomas account for 0.2% of all

malignancies diagnosed in the United States , and

the adjusted incidence rate for all bone and joint

malignancies is 0.9 per 100,000 persons per year,

while the 5-year overall survival rate is 67.9% .

The age specific incidence rates of bone sarcomas

typically show a bimodal distribution, with a first peak

occurring in the second decade, and a second peak

occurring in patients older than sixty years of age.

Epidemiology & incidence children are frequently affected .

The most frequently diagnosed histologic subtypes

were :

In adults, over 40% of primary bone cancers are

chondrosarcomas. This is followed by

osteosarcomas (28%), chordomas (10%), Ewing

tumors (8%), and malignant fibrous

histiocytoma/fibrosarcomas (4%). The remainder

of cases are several rare types of bone cancers.

In children and teenagers (those younger than 20

years), osteosarcoma (56%) and Ewing

tumors (34%) are much more common than

chondrosarcoma (6%).

Epidemiology & incidence

Causes & Risk factors

The cause of bone tumors is unknown.

Most people with bone cancers do not

have any apparent risk factors.

1-Genetic disorders A very small number of bone cancers

(especially osteosarcomas) appear to be

hereditary and are caused by defects

(mutations) in certain genes.

e.g. Li-Fraumeni syndrome osteosarcoma

- Rothmund-Thomson syndrome.

- Familial retinoblastoma syndrome .

Causes & Risk factors

2) multiple osteochondromas .

3) paget disease (pre-cacerous

lesion) .

4) Radiation

5) Bone marrow transplantation .

6) Injuries .

Classification of bone tumors

Bone tumors may be classified

as “primary tumors", which originate in bone

or from bone-derived cells and tissues,

and “secondary tumors" which originate in

other sites and spread ( metastatic ) .

Most classifications of bone tumours are based

on the recognition of the dominant cell tissue

(histopathology ) in the various lesions .

the current WHO classification (2002)includes a

total of 45 main bone tumor types .

WHO CLASSIFICATION OF

BONE TUMOURS

Bone-forming tumors (osteogenic )

Cartilage forming tumors (chondrogenic )

Giant-cell tumor

Marrow tumors

Vascular tumors

Other connective tissue tumors

Other tumors

Secondary malignant tumors of bone

Histologic Type Benign Malignant

Chondrogenic (22%) Osteochondroma Chondrosarcoma

ChondromaDedifferentiated

chondrosarcoma

ChondroblastomaMesenchymal

chondrosarcoma

Chondromyxoid

fibroma

clear cell

chondrosarcoma

Osteogenic (19%) Osteoid osteoma Osteosarcoma

Osteoblastoma

Fibrogenic

Desmoplastic fibroma

fibrosarcoma

notochordal tumors Chordoma

Histiocytic originBenign Fibrous

histiocytoma

Malignant fibrous

histiocytoma

Ewing’s sarcoma/PNET

Giant cell tumorMalignant Giant cell

tumor

Hematopoietic (40%) Myeloma

Malignant lymphoma

Joint lesions Synovial chondromatosis

Vascular Hemangioma Hemangioendothelioma

Hemangiopericytoma,

angiosarcoma

Lipogenic Lipoma Liposarcoma

Neurogenic Neurilemmoma

Smooth muscle tumors Leiomyoma Leiomyosarcoma

Miscellaneous tumors Adamantinoma

Metastatic malignancy

Tumours of unidentified

neoplastic nature

Aneurysmal bone cyst

Simple cyst

Fibrous dysplasia

Langerhan’s cell

histiocytosis

Chest wall hamartoma

Osteofibrous dysplasia

Radiographic features that may help differentiate benign from malignant lesions

Distribution of bone tumors in long bones

Epiphyseal lesions

chondroblastoma

Giant cell tumor

Metaphysealintramedullary

lesions:

Osteosarcoma

Chondrosarcoma

Aneurysmal bone cyst

Distribution of bone tumors in long bones

Metaphyseallesions centered

in the cortex:

Nonossifying fibroma (NOF)

Osteoid osteoma

Metaphysealexostosis:

Osteochondroma

Distribution of bone tumors in long bones

Diaphysealintramedullary

lesions:

Ewing’s sarcoma

Lymphoma

Myeloma

Enchondroma

Diaphyseallesions centered

in the cortex:

Adamantinoma

Osteoid osteoma

Distribution of bone tumors in long bones

Diagnosis of bone tumors

Signs and Symptoms of Bone Cancer

• - Pain in the bone.

• - Tenderness and swelling near the area

• which is affected.

• - The affected bone may break (pathologic #)

“may be the first and only clinical sign.”

• - Tiredness.

• - Weight loss which is unintentional.

Diagnosis of bone tumors

Imaging tests to detect bone cancer :

- X-rays >>> Most useful of all imaging

techniques.

>> There might be obvious

abnormality of the bone:

1 * Cotrical thickening

2 * Discrete lump

3 * Cyst

4 * Ill-defined destruction

- CT AND MRI

Diagnosis of bone tumors

- Biopsy There are three ways:

1.Needle biopsy: Must be performed by

experienced personal.

2. Open biopsy: most reliable way of

obtaining a representative sample.

3. Excisional biopsy: for benign tumors.

Staging of bone tumors

Staging is the process of finding out how

far the cancer may have spread.

This is very important because the type of

treatment and the outlook for recovery

(prognosis) depend on the stage of the

cancer.

Staging of bone tumors

In treating tumors we are facing two

conflicting principles:

1. Lesion must be removed widely to

ensure it doesn’t recur.

2. Damage must be kept minimal.

Staging of bone tumors

The balance between the 2 conflicting objectives depends on knowing:

1. How the tumor behaves (Aggressiveness)

2. How far it has spread.

The answers to these two questions are embodied in the staging system of Enneking.

Tumor

Benign

Latent

Active

Aggressive

Malignant

Low Grade

High Grade

Aggressiveness

Enneking Staging system of

bone tumors

Benign Tumors

Latent Well defined margin. Grows

slowly and then stops.

Remains static/heals

spontaneously E.g Osteoid

osteoma

Active Progressive growth limited

by natural barriers.

Not self limiting. Tendency to

recur E.g Aneurysmal Bone

cyst

Aggressive Growth not limited by

natural Barriers E.g Gaint cell

tumor

Enneking Staging system of

bone tumors

Malignant Tumors

Low Grade Moderatly aggressive and

takes a long time to

metastasize

High Grade Very aggressive and

metastasize early

Spread

Assuming that there is no metastases, the

local extent of the tumor is the most

important factor in deciding how much

tissue to be removed.

Spread

Intracompartmental

Extracompartmental

Spread

Lesions that are confined to an enclosed

space (e.g Bone cavity, joint cavity or

muscle group within its fascial envelope)

are called Intracompartmental.

Lesions that extend into interfascial or

extrafascial with no natural barrier to

proximal or distal spread are called

Extracompartmental. (E.g pelvis, axilla)

Surgical stage

Staging the tumor is an important step

towards selecting the best operation

suited to the patient.

Bone sarcomas are divided as follows:

1. Stage 1: All low grade sarcomas

2. Stage 2: Histologically high grade lesions

3. Stage 3: Sarcomas which have

metastasized.

Surgical stages described by Enneking

Stage Grade Site Metastases

IA Low Intracompart

mental

No

IB Low Extracompart

mental

No

IIA High Intracompart

mental

No

IIB High Extracompart

mental

No

IIIA Low Intra/extraco

mpartmental

Yes

IIIA High Intra/extraco

mpartmental

Yes

Primary malignant bone

tumors

Bone cancers are differentiated into types depending on the cell type in which the cancer started. Given below are some of the common types of bone cancer:

1) osteosarcoma

2) chondrosarcoma

3) Ewing’s sarcoma

Multiple myeloma

Metastatic bone diseases

Primary malignant bone

tumors

Primary bone malignancy Frequency (%)

35.1

16.0Ewing’s sarcoma

8.4Chordoma

Osteosarcoma

Osteosarcoma Also called Osteogenic Sarcoma .

Is the most common primary bone cancer.

Osteosarcomas is a mesenchymally derived

malignant tumor that produces

osteoid and/or bone.

This cancer starts in the

bone cells.

Osteosarcoma It most often occurs in young people

between the ages of 10 and 30, but

about 10% of osteosarcoma cases

develop in people in their 60s and 70s.

is more common in males than females.

may affect any bone but most

commonly involves the

long-bone metaphyses,

especially around the knee

and at the proximal end of

the humerus.

Osteosarcoma

They can be:

INTRAMEDULLARY OS

INTRACORTICAL OS

JUXTACORTICAL OS

In its classic (intramedullary) form,

osteosarcoma is a highly malignant tumour

arising within the bone and spreading rapidly

outwards to the periosteum and surrounding

soft tissues .

Tumor is located at the typical metaphyseal site. The tumor shown in A is largely restricted to bone, whereas that illustrated in B is accompanied by massive soft tissue extension.

Osteosarcoma invasive, variable histology; frequent

metastases without treatment

painful, poorly defined swelling

Pathological fracture is rare.

x-ray shows

characteristic periosteal elevation and

spicule formation representing tumour

extension into periosteum .

The endosteal margin is poorly defined.

sunburst’ effect and Codman’s triangle

.

Osteosarcoma

Osteosarcoma (a) The metaphyseal site; increased density, cortical

erosion and periosteal reaction are characteristic.

(b) Sunray spicules and Codman’s triangle; (c) the same patient after

radiotherapy. (d) A predominantly osteolytic tumour.

Osteosarcoma

Osteosarcoma

MRI

examination: coronal, sagittal and axial scans

showing the intra-and extra-osseous extensions of

the tumour and its proximity to the neurovascular

bundle.

Osteosarcoma

MRIT1WI - Low/heterogenous signal intensityT2WI - High signal intensityConstrast - enhancing medullary cavity and solid

components.STIR - High signal intensity and helps in assessing

involvement of neurovascular bundles and muscles.

Osteosarcoma treatment: complete resection (limb

salvage, rarely amputation),

chemotherapy

survival “ 70%

Osteosarcoma – operative

treatment Postoperative x-

rays showing an

endoprosthetic replacement

following wide

resection of the lesion

Variants Of Osteosarcoma

1) Juxtacortical (parosteal)

low-grade sarcoma situated on the

surface of one of the tubular bones,

usually at the distal femoral or proximal

tibial metaphysis.

Slightly older age group.

X-ray shows a dense bony mass on

the surface of the bone or encircling it;

the cortex is not eroded and usually a

thin gap remains between cortex and

tumour

Parosteal osteosarcoma (a,b) X-rays show an

ill-defined extraosseous tumour – note the linear gap

between cortex and tumour.

Juxtacortical osteosarcomaof upper femur. There is only minimal involvement of the cortex

Juxtacortical osteosarcomalarge extracortical component

Juxtacortical osteosarcoma--Moderately atypical spindle tumor cells grow between irregularly shaped bone trabeculae

Variants Of Osteosarcoma

1) Juxtacortical (parosteal)

Treatment

- For a low-grade parosteal osteosarcoma,

wide excision without adjuvant therapy is

sufficient to ensure a recurrence rate

below 10 per cent.

- Dedifferentiated parosteal osteosarcoma

should be treated in the same way as

intramedullary sarcoma.

Variants Of Osteosarcoma

2) PERIOSTEAL OSTEOSARCOMA

It is more like an intramedullary

osteosarcoma, but situated on the

surface of the bone

Upper tibial shaft or femur.

X-ray shows a superficial defect of the

cortex, but

CT and MRI may reveal a larger soft-

tissue mass

Periosteal osteosarcoma. The white shining appearance is due to the high content of cartilage

periosteal chondrosarcoma. There is a predominance of myxochondroid areas

Bone formation in the center of a cartilaginous lobule in periosteal osteosarcoma

Variants Of Osteosarcoma

3) Osteosarcoma in Paget’s disease.

Osteosarcoma are of the polyostotic type

Pelvis, humerus, femur tibia & skull.

Large number of osteoclasts alternating

with atypical osteoblast.

X-ray shows the usual features of Paget’s

disease, but with areas of bone destruction

and soft-tissue invasion.

This is a high-grade tumour most patients have pulmonary metastases by the time the tumour is

diagnosed

PAGET’S SARCOMA

Proximal femur shows

thickened cortical and

medullary bone

characteristic of

underlying paget’s

disease with a large

hemorrhagic tan-white

sarcomatous tumor that

has broken through cortex

PAGET’S SARCOMA

High grade osteosarcoma permeating abnormal

bone seen in Paget’s disease which is thickened

and lined by osteoclasts

Variants Of Osteosarcoma

3) Osteosarcoma in Paget’s disease.

Treatment

Even with radical resection or amputation

and chemotherapy the 5-year survival

rate is low.

If the lesion is definitely

extracompartmental, palliative treatment

by radiotherapy may be preferable;

- chemotherapy is usually difficult because

of the patient’s age

Chondrosarcoma

Chondrosarcoma Chondrosarcoma is malignant cartilaginous tumor and the second

most common malignant tumors originating in bone.

Arise de novo or from pre-existing benign cartilagenous tumor

i.e. enchondroma or osteochondroma

accounts for about 20% of bone tumors and is diagnosed in

approximately 600 patients each year in the United States.

The highest incidence is in the fourth and fifth decades.

men are affected more often than women.

These tumours are slow-growing and are usually present for many

months before being discovered .

Patients may complain of a dull ache or a gradually enlarging

lump. Medullary lesions may present as a pathological fracture.

Chondrosarcoma

Most common bones involved are

metaphysis of long tubular bones, mostly in

the lower limbs (45%),

pelvis (25%),

ribs (8%),

spine (7%),

scapula (5%),

sternum (2%)other bones

Despite the relatively frequent occurrence of benign cartilage tumours in the small bones of the

hands and feet, malignant lesions are rare at these sites

Chondrosarcoma Patients with multiple hereditary exostoses, Ollier's disease

and Maffucci's syndrome have a higher risk for malignant

transformation of a cartilaginous lesion.

DIAGNOSTIC FEATURES OF SECONDARY MALIGANT CHANGE

OF A BENING CARTILAGE TUMOR INDUCES :- Evidence of soft tissue calcification or

a soft tissue mass.

- Endo-osteal erosion and permeative

features in an enchondroma including

areas of lysis.

- Growth in a previously stable exostosis

- Expansion of the cartilage cap of an exoxtosis

Chondrosarcoma(classification )

•central

•peripheralTheir location in

the bone

•Primary chondrosarcoma

•Secondary chondrosarcoma

Whether they develop without

or with precedent

•Conventional chondrosarcoma

•Clear cell chondrosarcoma

•Myxoid chondrosarcoma

•Mesenchymal chondrosarcoma

•Dedifferentiated chondrosarcoma

The predominant cell type in the

tumor

Chondrosarcomas take various

forms, according to:

Chondrosarcoma(classification )

Central chondrosarcoma

Also called

The tumor develops in the

medullary cavity of either tubular

or flat bones .

lobulated., translucent, bluish

whitish cartilaginous mass within

medullary cavity

accounting for more than 90 %

of chondrosarcomas

Most commonly at the proximal

end of the femur or in the

Innominate bone of the pelvis.

Typical chondrosarcoma

central Chondrosarcoma

large mass at the time of diagnosis, usually over 4 cm in diameter in 50% of cases.

Osteolytic lesion (50%)

intralesional calcification(s): 60-78% (rings and arcs calcification or popcorn calcification)

endosteal scalloping

affects more than two thirds of the cortical thickness (c.f. less than 2/3 in enchondromas)

moth eaten appearance or permeativeappearance in higher grade tumours

cortical remodelling, thickening and periosteal reaction are also useful in distinguishing between an enchondroma and low grade chondrosarcoma

Radiographic appearance

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Typical x-ray of a central

chondrosarcoma of the femur

secondary chondrosarcoma

in inferior pubic ramus

CT : In as many as 90% of cases, tumors appear as

lucent areas containing chondroid matrix calcification. Endosteal scalloping and cortical destruction are frequently easier to appreciate on CT scans than on radiographs.

CT scanning may be used to guide percutaneous biopsy

MRI : T1: low to intermediate signal

T2: very high intensity in non mineralised/calcified portions

gradient echo/SWI: blooming of mineralised/calcified portions

T1 C+ (Gd) most demonstrate heterogeneous moderate to

intense contrast enhancement. enhancement can be septal and peripheral rim-

like corresponding to fibrovascular septationbetween lobules of hyaline cartilage

central Chondrosarcoma

central Chondrosarcoma

Histologically, chondrosarcomas are

graded on a scale of I–III based primarily

on nuclear size, staining and cellularity.

central Chondrosarcoma

Histologically, chondrosarcomas are

graded on a scale of I–III based primarily

on nuclear size, staining and cellularity.

Wide range of differentiation and graded

into:

- well differentiated

- moderately differentiated

- poorly differentiated

central Chondrosarcoma

Well-differentiated chondrosarcoma. The

tumor has a distinctly lobulated quality

Well differentiated- High-power appearance

of grade 1 chondrosarcoma. A few doubly

nucleated cells and moderate atypia .

Moderately differentiated -High-power appearance of grade 2

chondrosarcoma with necrosis . The nuclei

are crowded and hyperchromatic

Poorly differentiated

Chondrosarcoma(classification )

Peripheral chondrosarcoma

Tumor is present on the surface of bone.

May arise de-novo or from cartilaginous cap of

preexisting osteochondroma .

X-rays show :

the bony exostosis, often surmounted by clouds of

patchy calcification

in the otherwise unseen lobulated cartilage cap.

MRI is the best means of showing the size and internal

features of the cartilage cap.

Peripheral chondrosarcoma of femur

resulting in a huge exophytic mass .

Chondrosarcoma(classification )

Juxtacortical (periosteal ) chondrosarcoma

the lesion appears as an excrescence on the surface of one

of the tubular bones – usually the femur.

It arises from the outermost layers of the cortex, deep to the

periosteum .

Cartilaginous lobular pattern with areas of:

spotty calcification

endochondral ossification

Closely related to periosteal osteosarcoma .

Chondrosarcoma(classification )

Clear-cell chondrosarcoma

• Behaves as low-grade malignancy

• Can undergo dedifferentiation

• Location: proximal end of femur and humerus

Clear cell chondrosarcoma

with faint lobulation,

woven bone, and clear cells

Chondrosarcoma(classification )

Mesenchymal chondrosarcoma

This is an equally controversial entity.

It tends to occur in younger individuals .

and in about 50 per cent of cases the tumor lies in the

soft tissues outside an adjacent bone.

The x-ray appearances are similar to those of the

common types of chondrosarcoma

but the clinical behavior of the tumor is usually more

aggressive.

Histology shows a mixture of mesenchymal cells and

chondroid tissue

Chondrosarcoma(classification )

Dedifferentiated chondrosarcoma:

Worst prognosis.

Age/sex: sixth decade/ M:F =1:1.

Bones involved: pelvis, femur.

Poorly differentiated sarcomatouscomponent at periphery of otherwise typical low-grade chondrosarcoma

usually central type

can be peripheral

Chondrosarcoma(treatment)

• These tumors are not generally sensitive to chemotherapy and radiotherapy.

• Surgery is the only reliable treatment with wide excision and prosthetic replacement, for these tumors.

• CHONDROSARCOMA IN SITU:

can be treated with intra lesional excision

coupled with adjuvants like phenol or

cryotherapy instead of wide excision .

Chondrosarcoma(prognosis)

• Most of pulmonary metastasis or local reccurences occur with in first five years of presentation.

• Survival rates at the end of 10 years were 89% for grade 1 ,

53% for grade2

and 38% for grade3 chondrosarcomas .

Ewing’s sarcoma

Ewing’s sarcoma Ewing’s sarcoma (ES) was first described by James Ewing

in 1921 as

a "diffuse endothelioma of bone"

He observed that this highly aggressive bone

cancer was remarkably sensitive to radiation

therapy.

Ewing sarcoma, a highly malignant primary bone tumor

that is derived from red bone marrow second most

common primary bone tumour of childhood.

Ewings sarcoma is thought to be of either neuro-

ectodermal or stem cell origin

All Ewings sarcoma’s are considered high grade malignancy

Ewing’s sarcoma

9% of primary bone sarcomas

4th most common primary malignancy of bone but

2nd most common below 30yrs.

Age Group – 95% patients age between 5 to 30 yrs

- of these most range between 5 to 15 yrs

Sex - slight male predilection – 60%

More common in Whites (95%)

No known predisposing factor

Chromosomal translocation – t(11;22)(q24;q12)

leading to fusion of EWS and FLI gene.

also t(21;22) and t(7;22)

Ewing’s sarcoma Affected bones include,

long bones: 50-60%,

femur: 25%,

tibia: 11%,

humerus: 10%,

flat bones: 40%,

pelvis: 14%,

scapula, ribs: 6%

As far as location within

long bones, the tumor is

almost always metaphyseal

or diaphyseal.

Ewing’s sarcoma

The patient presents with pain

– often throbbing in character –

and swelling. May also have systemic symptoms:

Fever

Anemia

Weight loss

Elevated WBC & ESR,LDH

Pathological fracture .

Ewing’s sarcoma

Plain Radiography• Typical presentation: ill-defined

osteolytic lesion with a moth-eaten orpermeative type of bone destruction,irregular cortical destruction andaggressive periostitis.

• reactive sclerosis, irregular periosteal reaction and soft tissue mass.

• Ewing sarcomas tend to be largepoorly marginated tumours,with over 80% demonstratingextension into adjacent soft tissues.

fusiform layers of bone

around the lesion • laminated (onion skin) periosteal

reaction: 57% (onion-peel effect .

imaging

Ewing’s sarcomaimaging

Ewing’s tumour

Examples of Ewing’s

tumour in

(a)the humerus, (b) the

mid-shaft of the fibula

note the ‘onion-peel’

(b)effect in

themiddiaphysis.and (

(c) the lower end of the

fibula.

Hair-on-end periosteal

reaction

Onion skin formation

Metatarsal

involvement with

moth-eaten

appearance,

periostitis Involvement of long bone with

lamellated appearance,

saucerisation, cortical breach,

periostitis

Ewings sarcoma with extensive soft tissue

involvement

Ewing’s sarcomaimaging

Ewing’s sarcoma

• Greyish-white to pink in color

• soft, friable

• Often of semi-liquid consistency

macroscopy

• sheets of small dark polyhedral cells with no regular arrangement and no ground substance are seen.

microscopy

pathology

Ewing’s sarcomapathology

There is a

monotonous pattern of small round cells

clustered around blood vessels

Differential diagnosis

Osteosarcoma

Lymphoma

Leukemia

Osteomyelitis

PNET

Ewing’s sarcomatreatment

best results are achieved by a combination

of :

- a course of preoperative neo-adjuvant

chemotherapy;

- then wide excision if the tumor is in a

favourable site,

- or radiotherapy followed by local

excision if it is less accessible;

- and then a further course of

chemotherapy for 1 year.

Ewing’s sarcomaprognosis

The prognosis is always poor , esp. if

Proximal segment involvement

Sacral involvement

Patients above 18 yrs

Increased LDH and ESR

Size greater than 8cm

The prognosis has improved dramatically since the introduction of multi-agent chemotherapy

– from an erstwhile 10 per cent survival rate to the current 70 per cent for patients with nonmetastatic

Ewing’s sarcoma.

NON-HODGKIN’S LYMPHOMA(RETICULUM-CELL

SARCOMA )

NON-HODGKIN’S LYMPHOMA(RETICULUM-CELL SARCOMA)

Rare malignant condition that accounts for less than

5% of all primary bone tumors .

Like Ewing’s sarcoma, this is a round-cell tumor of

the reticuloendothelial system.

It occurs in the second to seventh decades, with a

peak age of occurrence from 45 to 75 years. M>F

It has also been called reticulum cell sarcoma,

malignant lymphoma of the bone, and more

recently osteolymphoma.

Distinguishing primary bone lymphoma from other

bone tumors is important because the former has a

better response to therapy and a better prognosis.

NON-HODGKIN’S LYMPHOMA(RETICULUM-CELL SARCOMA)

It is usually seen in sites

with abundant red marrow:

the flat bones, the spine and

the long-bone metaphyses .

X-ray shows a mottled

area of bone destruction in

Areas that normally contain

red marrow;

the radioisotope scan

May reveal multiple

lesions.

Non-Hodgkin’s lymphoma

(a) X-ray showing a rather nondescript

moth-eaten appearance of the ilium.

(b) MRI reveals the extent of the soft-tissue

lesion.

Multiple myeloma

Multiple myeloma Multiple myeloma is the most common primary malignant

neoplasm of the skeletal system. The disease is a malignancy of plasma cells “plasma cell myeloma,”

IT is a malignant B-cell lymphoproliferative disorder of the marrow, with plasma cells predominating, resulting in the overproduction of monoclonal immunoglobulins .

The effects on bone are due to marrow cell proliferation and increased osteoclastic activity, resulting in osteoporosis and the appearance of discrete lytic lesions throughout the skeleton.

Remember that myeloma is one of the commonest causes of osteoporosis and vertebral compression fracture in men over the age of 45 years.

Average age is 50-70 yrs

Much more common in men than women .

Multiple myeloma

Most commonly affected bones are:

vertebrae (66%),

ribs (45%),

skull (40)%,

shoulder (40%),

pelvis (30%),

and long bones (25%).

Multiple myeloma Associated features of the marrow-cell disorder are

- plasma protein abnormalities, and Bence-Jones protein in 40-60% of pts .

- increased blood viscosity and anaemia.

- Bone resorption leads to hypercalcaemia in 1/3 of cases.

Late secondary features are

- due to renal dysfunction and spinal cord or root compression

caused by vertebral collapse.

presents with :

weakness, backache, bone pain or a pathological fracture.

Hypercalcaemia may cause symptoms such as

thirst, polyuria and abdominal pain .

Multiple myeloma

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Plain Radiography• A full skeletal survey is required

for proper evaluation.

• No. of lytic lesions is directlyproportional to the tumor load.

• Classical lesions are well definedrounded / punched out lytic lesions scattereddiffusely among the involved bones.

• Such lesions in skull gives 'pepper pot‘or 'swiss cheese' appearance,however the occipital bone is spared.

• Multiple deformed vertebral bodies.

• Diffuse osteopenia &osteoporosis .

• No periosteal bone formation.• Medullary involvement in the

form of endosteal scalloping.

imaging

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imaging

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imaging

CT Computed tomography (CT) scanning readily

depicts osseous involvement in myeloma.

CT allowed a more accurate evaluation of areas at risk of fracture.

Tool of choice utilised in image guided spinal or pelvic bone biopsy.

MRI Most sensitive imaging modality at detecting

diffuse and focal multiple myeloma in the spine, as well as the extra-axial skeleton

Mainly bone marrow based lesions.

T1WI - Low signal intensity

T2WI and STIR - High signal intensity.

Show enhancement on contrast enhanced images.

Lab findings Anemia, leukopenia, thrombocytopenia

ALb, reversed A:G ratio

serum creat, uric acid, urea

Abnormal coagulation

Serum Ca

Proteinuria and cast

ESR

LOW NORMAL ALKALINE PHOSPHATASE

Red cells show rouleaux formation

BENCE-JONES PROTEIN in urine in 30%

Serum electrophoresis

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Major criteria: A biopsy-proven plasmacytoma.

A bone marrow sample

showing 30% plasma cells.

Elevated monoclonal Ig levels

in the blood or urine

Minor criteria: A bone marrow 10%-30% plasma cells.

Minor monoclonal Ig levels in blood or urine

Imaging --- holes in bones due to tumor growth

Antibody levels (not produced by the cancer cells) in the blood are abnormally low.

Diagnosis

Multiple myeloma

Durie-Salmon system :

clinical stage of disease (stage I, II, or III) is based

levels of M protein,

number of lytic bone lesions,

hemoglobin values and serum calcium levels.

Stages are further divided (A/B) according to renal function

International Staging

System (ISS)

new, simpler, more

cost-effective :

beta 2-micro

globulin (β2-M) and

albumin

staging

Multiple myeloma Stage Durie-Salmon Criteria ISS Criteria

I • Hb >10 g/dL

• S. Ca++≤12 mg/dL

• x-ray, normal bone stru.

or solitary bone plasmacytoma

• Low M-component production rate —

( IgG <5 g/dL; IgA <3 g/dL)

• Bence Jones protein <4 g/24 h

β2-M < 3.5 mg/dL and

albumin ≥3.5 g/dL

II* Neither stage I nor stage III Neither stage I nor stage III

III •Hb <8.5 g/dL

•S. Ca++

>12 mg/dL

•Advanced lytic bone lesions

•High M-component production rate —

(IgG>7 g/dL; IgA>5 g/dL)

•Bence Jones protein >12 g/24 h

β2-M ≥ 5.5 mg/dL

*Stage II = β2-M <3.5 or β2-M 3.5 – 5.5 mg/dL, and albumin <3.5 g/dLsub classification A) S. Creat.<2.0 mg/dl &

B) S. Creat.>2.0 mg/dl

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Management

Supporative :- The immediate need is for pain

control and, if necessary,

treatment of pathological

fractures.

- correction of fluid balance

and hypercalcaemia.

- antibiotic prophylaxis is important as there is a

higher than usual risk of infection and wound

breakdown.

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Management

Radiation :- Myeloma is radiosensitive

- Eventually looses its susceptibility

- Relieves pain

- Can be used for control of local disease (Solitary

plasmacytomas )

- Total body irradiation not advised .

Surgical options :

- Compression of intra-spinal nerves >>>

laminectomy, removal of myelomatoustissue

and post-op irradiation

- In cases with instability spinal fusion

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Management

Systemic anti-myeloma treatment :- alkylating cytotoxic agents (e.g. melphalan) with

Prednisone (has stem cell toxicity ) .

If stem cell transplantation is NOT planned :

- Melphalan/prednisone/thalidomide (MPT)

- Bortezomib/melphalan/prednisone (VMP)

- Thalidomide/dexamethasone(thaldex)

- levalidomide/low dose dexa (Revlodex)

If stem cell harvest is planned

- Bortezomib/thalidomide/dexamethasone (VTD)

- VCD -VELCADE/Cyclophosphamide/Dexa

- VRD - VELCADE/Revlimid/Dexa

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Management

Newer chemotherapy drugs for MM:

- Pomalidomide

- Next-generation proteasome

inhibitors- carfilzomib, NPI-0052

- Doxil-pegylated liposomal doxorubicin

- Histone deacetylase (HDAC) inhibitors

ex. vorinostat, panobinostat

- Monoclonal antibodies-elotuzumab

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Management

Maintenance therapy :

Alpha Interferon

Prednisone

Melphalan

Velcade

Revlimid

Dexamethasone

The prognosis in established cases is poor, with

a median survival of between 2 and 5 years.

Prognosis

Rajkumar et al. Mayo Clin Proc. 2002;77:814

Management of Complications

• UREMIA: rehydratation, diuretics,steroids,antibiotics if renal infection is suspected, hemodialysis if these measures fail.

• HYPERCALCEMIA: rehydratation, steroids, bisphosphonates, diuretics.

• PARAPLEGIA: decompressive laminectomy, radiotherapy, chemotherapy.

• BONE LESIONS: if painful and localised, chemo or local radio-therapy, analgetics, biphosphonates.

• SEVERE ANEMIA: transfusions, erytropoetin

• HYPERVISCOSITY SYNDROME: plasmapheresis, correction of hypercalcemia.

• BLEEDING: platelet concentrates, fresh frozen plasma

• INFECTIONS: antibiotic treatment

Adamantinoma Rare primary malignant bony tumor, only approximately 200 cases have been

reported.

The tumor occurs almost exclusively in the long bones; tumors in the tibia account for more than 80% of cases. The diaphyseal region is the area most commonly affected. but is occasionally found in other long bones.

Typically presents in the 2nd to 3rd decades as a locally aggressive mass 3-15 cm in diameter .

Adamantinoma is a low-grade tumor which metastasizes late

It may present as a solitary focus or multicentric lucencies or slightly expansileosteolytic lesion

May extend into the marrow cavity.

Lesions tend to have an eccentric epicenter and a lack of periosteal reaction.

usually no periosteal reaction is noted in the surrounding bone

Long-standing tumors produce marked cortical thickening and spool-shaped bulges of the outer cortex in an eggshell fashion.

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X-ray shows a typical

bubble-like defect in the anterior tibial

cortex; sometimes

there is thickening of

the surrounding

bone.

Imaging

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MRI two morphologic patterns are

seen :- a solitary lobulated focus - multiple small nodules in one or more foci.

In some patients separated tumour foci may be seen, defined as foci of high signal intensity on either T2- or T1-weighted contrast-enhanced images, interspersed with normal-appearing cortical or spongiousbone.

Fluid-fluid level may occasionally be seen.

C+(Gd): tends to show intense and homogeneous static enhancement, although there is no uniform dynamic enhancement pattern.

Imaging

Adamantinoma

If the diagnosis is made reasonably early,

wide local excision with a substantial margin of

normal bone is adequate .

- the gap is filled with a vascularized graft or a suitable

endoprosthesis, or managed by distraction

osteogenesis .

If there has been more than one recurrence, or if

the tumor extends into the surrounding soft

tissues, radical resection or amputation is

advisable.

metastatic Bone Diseases

metastatic Bone Diseases The skeleton is one of the commonest sites of secondary

cancer .

in patients over 50 years bone metastases are seen more

frequently than all primary malignant

bone tumours together. (Approximately 70% of all malignant

tumors are metastatic in origin. )

Metastases are usually osteolytic, and pathological

fractures are common .

Bone resorption is due either to the direct action of tumor

cells or to tumor-derived factors that stimulate osteoclastic

activity.

Osteoblastic lesions are uncommon; they usually occur in prostatic carcinoma.

metastatic Bone Diseases

Sites :

- The commonest sites for bone metastases

are the vertebrae, pelvis, the proximal half

of the femur and the humerus.

Sources :- The commonest source is carcinoma of the breast; next

in frequency are carcinomas of the prostate, kidney,

lung, thyroid, bladder and gastrointestinal tract.

- In about 10 per cent of cases no primary tumor

is found.

metastatic Bone Diseases

metastatic Bone Diseases Spread :

- Spread is usually via the blood stream .

- occasionally, visceral tumours spread directly to

adjacent bones (e.g. the pelvis or ribs).

metastatic Bone Diseases types :

- osteolytic metastases- sclerotic/osteoblastic metastases- mixed lytic and sclerotic metastases

Osteoblastic metastases Osteolytic metastases Mixed metastases

prostate carcinoma (most common) RCC Lung carcinoma (25%)breast carcinoma (may be mixed) Thyroid carcinoma Breast carcimoma (15%)transitional cell carcinoma (TCC) Pheochromocytoma carcinoma of cervixcarcinoid Wilms tumor testicular tumorsmedulloblastoma Ewings sarcoma Prostatic carcinoma (15%)neuroblastoma Carcinomas of GITmucinous adenocarcinoma of GIT Melanomalymphoma HCC

SCC of skin

Uterine carcinoma

metastatic Bone Diseases Imaging :

• little or no soft tissue mass associated with them• Usually no periosteal reaction• May appear as moth-eaten, permeative or geographic lesions• Indistinct zones of transition, no sclerotic margins and may be

sharply circumscribed or have indistinct borders• Lesions distal to elbows and knees - 50% are from lung and breast• Diffuse skeletal sclerosis or multiple round, well-circumscribed

sclerotic lesions - Prostate & Breast• Expansile and lytic (soap-bubbly) - RCC• Cookie-bite lesions of the cortices of long bones - Lung• Bone scans are extremely sensitive but not very specific• 10-40% of lesions will not be visible on plain film but will be positive

on bone scans• CT or MRI can be used to show findings in patients with negative

conventional radiographs and positive bone scans

metastatic Bone Diseases Imaging :

metastatic Bone Diseases

metastatic Bone Diseases treatment:

- By the time a patient has developed secondary deposits the

prognosis for survival is poor.

- Occasionally, radical treatment (combined chemotherapy,

radiotherapy and surgery) targeted at a solitary secondary

deposit and the parent primary lesion may be rewarding and even

apparently curative.

- but in the great majority of cases, and certainly in those with

multiple secondaries, treatment is entirely symptomatic.

Palliative care

metastatic Bone Diseases prognosis:

- Bauer (1995) has suggested useful criteria for assessing prognosis .

In his series of patients, survivorship at 1 year was as follows:

• of patients with 4 or 5 of Bauer’s criteria 50 per cent were alive

of patients with 2 or 3 criteria 25 per cent were alive

of patients with only 1 or none of the criteria,

the majority survived for less than 6 months and none were alive at 1 year.

BAUER’S POSITIVE CRITERIA FOR SURVIVAL

• A solitary metastasis

• No pathological fracture

• No visceral metastases

• Renal or breast primary

• No lung cancer

المراجع

Diagnostic Imaging -Imaging of Bone Tumors and

Tumor-Like Lesions_Techniques and Applications ,Editors: A. L. Baert, Leuven &M. Knauth, G ttingen

1sted.

Apley’s System of Orthopaedics and Fractures 9th ed

part 1 chapter 9 .

American cancer society

www.cancer.org/bonecancer.

المراجع http://www.slideshare.net/ARUNHALDIA/osteogenic-bone-

tumors.

http://www.slideshare.net/narmadaptiwari/bone-tumours-by-dr-narmada-prasad-tiwari

http://www.slideshare.net/kalhamadani/tumors-orthopedic

http://www.slideshare.net/ARUNHALDIA/osteogenic-bone-tumors?qid=1617d0c6-734b-445a-8762-d880bcebfb0b&v=default&b=&from_search=1

http://www.slideshare.net/upenderus/chondrosarcoma?qid=d5f04678-4690-4c04-aed2-e230aa79c0a1&v=default&b=&from_search=1

http://www.slideshare.net/vandana_rt/ewings-sarcoma-dr-vandana

http://www.slideshare.net/PruthvirajNistane/osteosarcoma-1

http://www.slideshare.net/xanthoid/an-approach-to-malignant-bone-tumors?qid=7476aa52-5476-460f-8119-eefe656419bc&v=qf1&b=&from_search=1

:عمل محمد عبدالستار عبدالجليل حمرة