The document provides a comprehensive overview of malignant bone tumors, including their classification, diagnosis, and treatment options. It discusses the different types of bone tumors, their epidemiology, risk factors, and the specific characteristics of tumors such as osteosarcoma and chondrosarcoma. Treatment approaches, including surgery and chemotherapy, are highlighted, along with the importance of accurate staging for prognosis and therapeutic strategy.

1. Malignant
Tumors of bones
Done by :
‫خالد‬‫عبدالجليل‬ ‫عبدالستار‬ ‫محمد‬
• Supervised by :
Dr : Ghazi AL-Ariki
‫اليمنية‬ ‫الجمهورية‬
‫العالي‬ ‫التعليم‬ ‫وزارة‬
‫تعز‬ ‫جامعة‬
‫الصحية‬ ‫العلوم‬ ‫و‬ ‫الطب‬ ‫كلية‬
‫بشري‬ ‫طب‬–‫العظام‬ ‫قسم‬

2. Malignant bone tumors

3. 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

4. Introdution
 Bones are classified according to their
shape-
 Long bone
 Flat bone
 Short bone.

5. 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

7. 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 )

8. Intro.
Histology of bone tissue

10. Osteoprogeniter cells &Osteoblast

11. Osteoclast

12. 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 .

13. 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

14. 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.

15. 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%).

16. Epidemiology & incidence

17. 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 .

18. Causes & Risk factors
2) multiple osteochondromas .
3) paget disease (pre-cacerous
lesion) .
4) Radiation
5) Bone marrow transplantation .
6) Injuries .

19. 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 .

20. 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

22. Histologic Type Benign Malignant
Chondrogenic (22%) Osteochondroma Chondrosarcoma
Chondroma
Dedifferentiated
chondrosarcoma
Chondroblastoma
Mesenchymal
chondrosarcoma
Chondromyxoid
fibroma
clear cell
chondrosarcoma
Osteogenic (19%) Osteoid osteoma Osteosarcoma
Osteoblastoma
Fibrogenic
Desmoplastic fibroma
fibrosarcoma

23. notochordal tumors Chordoma
Histiocytic origin
Benign Fibrous
histiocytoma
Malignant fibrous
histiocytoma
Ewing’s sarcoma/PNET
Giant cell tumor
Malignant Giant cell
tumor
Hematopoietic (40%) Myeloma
Malignant lymphoma
Joint lesions Synovial chondromatosis
Vascular Hemangioma Hemangioendothelioma
Hemangiopericytoma,
angiosarcoma

24. 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

25. Radiographic features that may help differentiate benign
from malignant lesions

26. Distribution of bone tumors
in long bones
Epiphyseal
lesions
chondroblastoma
Giant cell tumor
Metaphyseal
intramedullary
lesions:
Osteosarcoma
Chondrosarcoma
Aneurysmal bone
cyst

27. Distribution of bone tumors
in long bones
Metaphyseal
lesions centered
in the cortex:
Nonossifying
fibroma (NOF)
Osteoid osteoma
Metaphyseal
exostosis:
Osteochondroma

28. Distribution of bone tumors
in long bones
Diaphyseal
intramedullary
lesions:
Ewing’s sarcoma
Lymphoma
Myeloma
Enchondroma
Diaphyseal
lesions centered
in the cortex:
Adamantinoma
Osteoid
osteoma

29. Distribution of bone tumors
in long bones

31. 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.

32. 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

33. 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.

35. 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.

36. 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.

37. 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.

38. Tumor
Benign
Latent
Active
Aggressive
Malignant
Low Grade
High
Grade
Aggressiveness

39. 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

40. 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

41. 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

42. 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)

43. 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.

44. 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

45. 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

46. Primary malignant bone
tumors
Primary bone malignancy Frequency (%)
35.1
16.0Ewing’s sarcoma
8.4Chordoma

47. Osteosarcoma

48. 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.

49. 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.

50. 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 .

51. 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.

52. 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
.

53. 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.

54. Osteosarcoma

55. 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.

56. Osteosarcoma
MRI
T1WI - Low/heterogenous signal intensity
T2WI - High signal intensity
Constrast - enhancing medullary cavity and solid
components.
STIR - High signal intensity and helps in assessing
involvement of neurovascular bundles and muscles.

57. 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

58. 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

59. Parosteal osteosarcoma (a,b) X-rays show an
ill-defined extraosseous tumour – note the linear gap
between cortex and tumour.

60. Juxtacortical osteosarcoma
of upper femur. There is only
minimal involvement of the
cortex
Juxtacortical osteosarcoma
large extracortical component

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

62. 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.

63. 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

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

65. periosteal chondrosarcoma. There is a predominance of
myxochondroid areas

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

67. 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

68. 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

69. PAGET’S SARCOMA
High grade osteosarcoma permeating abnormal
bone seen in Paget’s disease which is thickened
and lined by osteoclasts

70. 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

71. Chondrosarcoma

72. 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.

73. 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

74. 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

75. Chondrosarcoma
(classification )
•central
•peripheral
Their 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:

76. 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.

77. Typical chondrosarcoma

78. 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 permeative
appearance in higher grade tumours
 cortical remodelling, thickening and
periosteal reaction are also useful in
distinguishing between an
enchondroma and low grade
chondrosarcoma
Radiographic appearance

79. centralChondrosarcoma
Radiographicappearance
Typical x-ray of a central
chondrosarcoma of the femur
secondary chondrosarcoma
in inferior pubic ramus

80. 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 septation
between lobules of hyaline cartilage
central Chondrosarcoma

81. central Chondrosarcoma
 Histologically, chondrosarcomas are
graded on a scale of I–III based primarily
on nuclear size, staining and cellularity.

82. 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

83. central Chondrosarcoma

84. Well-differentiated chondrosarcoma. The
tumor has a distinctly lobulated quality

85. Well differentiated- High-power appearance
of grade 1 chondrosarcoma. A few doubly
nucleated cells and moderate atypia .

86. Moderately differentiated -
High-power appearance of grade 2
chondrosarcoma with necrosis . The nuclei
are crowded and hyperchromatic

87. Poorly differentiated

88. 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.

89. Peripheral chondrosarcoma of femur
resulting in a huge exophytic mass .

90. 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 .

91. 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

92. 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

93. Chondrosarcoma
(classification )
Dedifferentiated chondrosarcoma:
 Worst prognosis.
 Age/sex: sixth decade/ M:F =1:1.
 Bones involved: pelvis, femur.
 Poorly differentiated sarcomatous
component at periphery of otherwise typical
low-grade chondrosarcoma
 usually central type
 can be peripheral

94. 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 .

95. 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 .

96. Ewing’s sarcoma

97. 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

98. 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)

99. 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.

100. 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 .

101. Ewing’s sarcoma
Plain Radiography
• Typical presentation: ill-defined
osteolytic lesion with a moth-eaten or
permeative type of bone destruction,
irregular cortical destruction and
aggressive periostitis.
• reactive sclerosis, irregular periosteal reaction
and soft tissue mass.
• Ewing sarcomas tend to be large
poorly marginated tumours,
with over 80% demonstrating
extension into adjacent soft tissues.
 fusiform layers of bone
around the lesion
• laminated (onion skin) periosteal
reaction: 57% (onion-peel effect .
imaging

102. Ewing’s sarcoma
imaging
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.

103. Hair-on-end periosteal
reaction
Onion skin formation

104. Metatarsal
involvement with
moth-eaten
appearance,
periostitis Involvement of long bone with
lamellated appearance,
saucerisation, cortical breach,
periostitis

105. Ewings sarcoma with extensive soft tissue
involvement

106. Ewing’s sarcoma
imaging

107. 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

108. Ewing’s sarcoma
pathology
There is a
monotonous pattern of small round cells
clustered around blood vessels

109. Differential diagnosis
 Osteosarcoma
 Lymphoma
 Leukemia
 Osteomyelitis
 PNET

110. Ewing’s sarcoma
treatment
 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.

111. Ewing’s sarcoma
prognosis
 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.

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

113. 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.

114. 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.

115. Multiple myeloma

116. 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 .

117. Multiple myeloma
 Most commonly affected bones are:
vertebrae (66%),
ribs (45%),
skull (40)%,
shoulder (40%),
pelvis (30%),
and long bones (25%).

118. 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 .

119. Multiple myeloma

120. Multiplemyeloma Plain Radiography
• A full skeletal survey is required
for proper evaluation.
• No. of lytic lesions is directly
proportional to the tumor load.
• Classical lesions are well defined
rounded / punched out lytic lesions scattered
diffusely 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

121. Multiplemyeloma imaging

122. Multiplemyeloma 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.

123. 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

124. Multiplemyeloma
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

125. 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

126. 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/dL
sub classification A) S. Creat.<2.0 mg/dl &
B) S. Creat.>2.0 mg/dl

127. Multiplemyeloma
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.

128. Multiplemyeloma
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 myelomatous
tissue
and post-op irradiation
- In cases with instability  spinal fusion

129. Multiplemyeloma
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

130. Multiplemyeloma
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

131. Multiplemyeloma
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

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

133. 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

135. 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 expansile
osteolytic 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.

136. Adamantinoma  X-ray shows a typical
bubble-like defect in
the anterior tibial
cortex; sometimes
there is thickening of
the surrounding
bone.
Imaging

137. Adamantinoma 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 spongious
bone.
 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

138. 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.

139. metastatic Bone Diseases

140. 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.

141. 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.

142. metastatic Bone Diseases

143. 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).

144. 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 cervix
carcinoid Wilms tumor testicular tumors
medulloblastoma Ewings sarcoma Prostatic carcinoma (15%)
neuroblastoma Carcinomas of GIT
mucinous adenocarcinoma of GIT Melanoma
lymphoma HCC
SCC of skin
Uterine carcinoma

145. 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

146. metastatic
Bone Diseases
 Imaging :

147. metastatic Bone Diseases

148. 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

149. 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

150. ‫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.

151. ‫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=d5f0
4678-4690-4c04-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

152. ‫عمل‬:
‫حمرة‬ ‫عبدالجليل‬ ‫عبدالستار‬ ‫محمد‬