SEMINAR 1

BONE TUMORS
BATCH 2015/2020 : YEAR 4 ROTATION 1
ANNAZATUL ZAIMAH – BMS15091520
CHAI XIAO SI – BMS15091561
CHRISTINE ANNE – BMS15091845
BRIDGET LO YEN – BMS15091785
ALAN KUOK CHE LONN – BMS14091236
CHIN IE XUAN – BMS15091568

WEDNESDAY , 3/10/2018
 LEARNING OUTCOMES
1. Types and classification of bone tumors
2. General principal of management in detail
– Surgery , Chemotherapy and Radiotherapy
3. Osteosarcoma
4. Giant cell tumor
5. Ewing sarcoma
6. Multiplr myeloma & bone metastasis
TYPES AND CLASSIFICATION
OF BONE TUMORS

ANNAZATUL ZAIMAH HUSSIN

BMS15091520
 BONES : OVERVIEW
• Osteoblasts – bone matrix synthesis and
initiating mineralization
• Osteocytes – calcium and phosphate
homeostasis for translation of mechanical
forces into biological activity
• Osteoclasts – mainly for bone resorption

Bone Homeostasis : A balance of bone

deposition by osteoblast and bone resorption
by osteoclasts
 BONES : PATHOLOGY
1. Developmental abnormalities
• Defects in extracellular structural protein
• Defects in metabolic pathways
• Defects in osteoclasts dysfunction
• Defects in mineral homeostasis
2. Fractures
3. Osteonecrosis / Avascular necrosis
4. Infections / Osteomyelitis
5. Bone tumors and tumor like lesions
 BONE TUMORS : OVERVIEW
• Most conditions are asymptomatic / detected as
incidental findings
• May present with pain / slow growing mass
• Diagnosis : patient age, neoplasm location and
radiologic appearance with biopsy and histologic
evaluation
• Benign tumors outnumber malignant tumors
except in elderly when bone tumors often
associated with malignancy.
 BONE TUMORS : TYPES
1) Bone-forming tumors
• Osteoblastoma, osteoid osteoma and osteosarcoma
2) Cartilage-forming tumors
• Osteochondroma, chondroma, chondroblastoma and
chondrosarcoma
3) Fibrous and Fibro-osseous tumors
• Fibroma, fibrous histiocytoma and fibrosarcoma
4) Miscellaneous tumors
• Giant cell tumors, Ewing sarcoma, chordoma
5) Hematopoietic origin
• Myeloma, malignant lymphoma
 MAJOR PRIMARY TUMORS INVOLVING BONES
HISTOLOGIC ORIGIN BENIGN MALIGNANT
OSTEOGENIC (19%) OSTEOBLASTOMA OSTEOSARCOMA
OSTEOID OSTEOMA
CHONDROGENIC ( 22%) OSTEOCHONDROMA CHONDROSARCOMA
CHONDROMA
CHONDROBLASTOMA
FIBROGENIC FIBROMA FIBROSARCOMA
NON OSSIFYING FIBROMA
FIBROUS HYSTIOCYTOMA
HEMATOPOIETIC (40%) MYELOMA
MALIGNANT LYMPHOMA
UNKNOWN ORIGIN (10%) GIANT CELL TUMOR
ANEURYSMAL BONE CYST
NEUROECTODERMAL EWING SARCOMA

NOTOCHORDAL BENIGN NOTOCHORDAL CHORDOMA

CELL TUMOR
 BONE TUMORS : CLASSIFICATION

BASED ON MODIFIED / REVISED

WHO CLASSIFICATION – SCHAJOWICZ (1994)
PRINCIPAL OF MANAGEMENT
SURGERY , CHEMOTHERAPY
AND RADIOTHERAPY

CHAI XIAO SI
BMS15091561
General principle of
management of bone
tumour
1) multidisciplinary management

• Orthopaedic surgeon
• Radiologist
• Pathologist
• Oncologist
• Rehabilitation nurses
 Diagnosis

Clinical diagnosis
Imaging
Lab investigation
Biopsy
⬇️
Treatment

Benign, Benign ,
Malignant
asymptomatic symptomatic
Neoadjuvant/adjuv
Surgical t
Conservatives Investigate &
curettage
 Clinical diagnosis
Personal details:
1)Age**
2)Sex

Complaints:
1)Pain
2)mass
 Imaging:
1)**X-ray:
:most useful imaging
:based on anatomical ,borders,bone
destruction, bone formation, periosteal
reaction of the tumour on X-ray can give a
clues to type of tumour
2)CT Scan
3)MRI
4)radionuclide scan/bone scan
5)angiography
Anatomical site of
tumour
Osteolytic tumour
 Osteoblastic tumours

Osteosarcoma
Periosteal reaction
 Lab investigation
1)full blood count:
Hemoglobin level:decreased
-> anemia due to marrow tumours : multiple
myeloma
ESR:abnormal high in multiple myeloma
2)prostate specific antigen
->rule out secondary metastasis from prostate
cancer
3)serum calcium(check in case of osteolytic
lesion)
:hyperparathyroidism, MM, metastasis
 Biopsy
Closed :
Opened:
FNAC
Open
Core
incisions
biopsy

Advantages& disadvantages?????
Enneking ‘s staging of malignant
tumour
 Treatment
Surgical treatment

Limb salvage Amputation

=resection of tumour + =resection of tumour
reconstruction of limb to without restoring the
restore function function of limb/lost of
the limb
 Resection
Suitable for:
method Removing

Debulking
tumour(left Benign
Intralesional
tumour tumour
behind)

Reactive
Benign
Marginal zone
tumour
+tumour

Tumour+re
1A,
active
Wide 2A+chemot
zone+norm
herapy
al tissue

Whole
Radical compartme 2A/2B
nt
 Reconstruction method
1)bone defect reconstruction
-vascularised /non vascularised bone graft
-custom-made implantation
-osteoarticular allograft, allograft-prosthetic composite
2)soft tissue /muscle transfer

CONTRAINDICATIONS FOR LIMB SALVAGE:

1)major neurovascular involvement
2)case presented with pathological fracture
3)infection
4)major skeletal involvement
5)skeletal immaturity
 Limb salvage Amputations

Long term survival rate

Advantages Better limb function than Simple procedure
amputation

Greater risk of infection,

wound dehiscence , flap
necrosis
Infection,chronic painful
Disadvantages Peri-prosthetic fracture
limb,phantom limb
Non union
Graft-host response
33% go to amputation
 Chemotherapy
Adjuvant chemotherapy:
Given after primary
resection have done(
maintainence of chemo for
another 6-12 months)
Rationale: to control the
microscopic metastasis
level
Regime: HIGH DOSE
METHOTREXATE
Neoadjuvant
chemotherapy:
Given before resection
done(usually 8-12 weeks
before surgery)
Rationale: to reduce size of
tumour for facilitate the
surgery

To access effectiveness of adjuvant therapy;

- examine the respected tumour necrosis, if it’s necrosis up to
90%= highly sensitive
- Means the drug for neoadjuvant can continued in adjuvant
- If not then, change another drugs for adjuvant therapy
 Radiotherapy
•Should be start after diagnosis before surgery
• Target lesion on tumours
• Radiotherapy+chemotherapy = 1+1>2
• Ewing tumour is highly sensitive tumour toward
radiotherapy
• Tumour that are not operable: big size, near major blood
vessel,marrow cells tumour, metastasis
• COMPLICATIONS:post-irradiation spindle cells sarcoma,
pathological fractures
OSTEOSARCOMA
CHRISTINE ANNE
BMS15091845
 Overview
• Definition
• Epidemiology
• Classification
• Risk Factors
• Clinical presentation
• Pathology
• Radiology Images
• Investigation
• Treatment
• Differential diagnosis
• References
 DEFINITION
• Osteosarcoma (also called osteogenic
sarcoma) is the most common type of cancer
that starts in the bones.
• Highly malignant tumor of mesenchymal origin
• Spindle shaped cells that produce osteoid
 EPIDEMIOLOGY
• Incidene : 1 to 3 per million per year
• Any age (75% in 12-25 years of age)
• Almost equal in both sexes but slightly more in
males
CLASSIFICATION
 RISK FACTORS
• AGE - The risk of osteosarcoma is highest for those between
the ages of 10 and 30, especially during the teenage growth
spurt.
• HEIGHT- Children with osteosarcoma are usually tall for their
age. This also suggests that osteosarcoma may be related to
rapid bone growth
• GENDER- Osteosarcoma is more common in males than in
females. Females tend to develop it slightly earlier, possibly
because they tend to have their growth spurts earlier
• ETHNICITY- Osteosarcoma is slightly more common in
African Americans and Hispanic/Latinos than in whites
• RADIATION- People who were treated with radiation therapy
for another cancer might have a higher risk of later developing
osteosarcoma in the area that was treated.
 Clinical presentation
• (A) Local Symptoms
• Pain in the affected bone ( on and off pain, worse at night)
• Swelling occur several weeks after pain starts, later on is
palpable and visible tumor mass, skin look shiny with
prominent veins, swelling warm and tender
• Decreased range of motion
• Lymphadenopathy is unusual
• Respiratory findings (cough, dyspnea, tachypnea) symptoms of
late disease and lung metastases
• (B) Systemic symptoms
• Fever, weight loss, night sweats (rare and not common)
PATHOLOGY
RADIOLOGY IMAGES
 DIAGNOSTIC PROCEDURES
(A) Laboratory Studies
• Basic hematology exam (CBC, coagulation profile, erythrocyte
sedimentation).
• Bone marrow biopsy is not a standard part of initial work up.
• Biochemistry (urea, creatinine, uric acid, liver function tests, ionogram,
CRP)
• Non-specific tumor markers: LDH (increased in 30%), ALP (increased in
40%)
(B) Imaging Studies
• Plain X-ray: is usually the first step, essential for diagnosis is to look for:
1. Localization of the tumor
2. Margins /limits of the lesion
3. Number of pathology bone lesions
4. Type of bone destruction (osteolytic,
sclerotic)
5. Presence of periostal reaction (Codman triangle) (Figure 6)
6. Soft tissue involvement
7. Relationship to the nearest joint
 DIAGNOSTIC PROCEDURES
• CT scan: of the primary localization of osteosarcoma as
well as CT of the chest show detailed cross-sectional
images of the body
• MRI : provide detailed images of the bone, show the
exact extent of a tumor as well as detailed view of the
bone marrow and soft tissue involvement.
• Bone scan
• PET scan can help show the spread of osteosarcoma to
the other organs of the body, but currently is not a part
of standard initial work up for osteosarcoma.
 TREATMENT
• (A) Chemotherapy
-Methotrexate, Doxorubicin, Cisplatin,
Ifosfamide
• (B) Surgery
 DIFFERENTIAL DIAGNOSTIC
• Factors important for differential diagnosis of bone tumors
• Age of the patient
• Localization, size and number of the tumor lesions
• Character of the tumor on imaging studies
• Soft tissue involvement
• Other bone lesions and diseases have to be distinguished from
osteosarcoma:
1. inflammatory lesions (chronic osteomyelitis)
2. stress fracture
3. benign bone lesions (giant cell bone tumor, osteochondroma…..)
4. other malignant bone tumors ( Ewing sarcoma,malignant lymphoma)
5. metastases to the bones (soft tissue sarcomas, renal tumors,
neuroblastoma)
GIANT CELL TUMOR
BRIDGET LO YEN
BMS15091785
 Giant Cell Tumour
• Benign bone lesion
• Usually solitary
• Locally aggressive
• Can undergo malignant transformation (5-
10%)
Incidence
10% of benign bone lesions
Not seen until after growth plate closes : age 20-40
yrs
Giant Cell Tumour
Clinical features

• Deep, persistent pain at

the end of long bone
• Swelling of an affected
area
• Risk for pathologic
fracture in the area of
tumour
 Giant Cell Tumour
Radiographic features
1.) X-rays
-Lytic lesion in
metaphysis/epiphysis
extending up to joint surface
-Eccentric
-Soap bubble appearance

2) Histology
-numerous multinucleated giant
cells
 Giant Cell Tumour
Investigation
1) X-rays
2) CT scans
3) MRI
4) Biopsy
Giant Cell Tumour
Treatment

Extended curettage
- Use of adjuvants, such as liquid
nitrogen, phenol,
polymethyl methacrylate
- 85-95% success rate of local control
Adjunctive measures
EWING SARCOMA
ALAN KUOK CHE LONN
BMS14091236
 Introduction
• Primary tumour of small round cells that affect bones
and soft tissues
• Ewing’s sarcoma tumour including:
- Ewing’s sarcoma (Bone-87%)
- Askin’s tumour
- Peripheral primitive neuroectodermal tumors (5%)
- Extraosseuos Ewing’s sarcoma (8%)
 Etiology
• thought to derive from cells of the neural crest, possibly
mesenchymal stem cells
• exact cell of origin of the Ewing sarcomas is unknown
• Translocation of EWSR1 (Ewing sarcoma breakpoint region 1)
with an ETS (E26 transformation-specific) transcription factor
gene occurs in more than 95% of Ewing sarcomas
• most common translocation seen in about 85% of all Ewing tumor
is the t(11;22) translocation
• alternative translocations include EWS-ERG t(21;22), EWS-ETV
t(7;22), and EWS-FEV t(2;22), all of which involve the ETS
family protein
 Clinical Features
• Localized pain
• Back pain, which may indicate a paraspinal, retroperitoneal, or
deep pelvic tumor
• Palpable mass
• Systemic symptoms of fever and weight loss, which often indicate
metastatic disease
• Anaemia
• lesions of the long bones can present with a pathologic fracture
• neuropathic pain
• petechiae or purpura that may be caused by thrombocytopenia due
to clinically significant bone marrow metastases
Locations of tumour
• Arise in medullary
cavity, usually of long
bones in the lower
extremities
• Most commonly occurs
in long bones and
pelvis (femur pelvis,
tibia, humerus)
• Involves metadiaphysis
of long bones
 Investigations
• Blood test
• Biopsy
• Imaging includes (X-ray, CT scan, MRI)
• Renal function test
• Liver function test
• Permeative (small holes) or
moth-eaten (mottled)
appearance
• Rare, can be sclerotic
• Periosteal reaction is common:
- lamellated (onion-skinning due
to successive laters of periosteal
development)
- sunburst or speculated
- Codman’s triangle (formed
between elevated periosteum with
central destruction of cortex
 Differential diagnosis
• Neuroblastoma
• Leukemia
• Reticulum cell sarcoma
• Multiple myeloma
• Osteomyelitis
• Eosinophilic granuloma
• Osteosarcoma
• Lymphoma
 Prognosis
• 60-75% five-year survival
• Predictors of poorer prognosis
- large tumour
- non-resectable lesions (in pelvis)
- older age
- elevated leukocyte count and sedimentation rate
at presentation
 Treatment and Management
• Chemotheraphy
- lasts 6-9 months and consists of alternating courses of 2
chemotherapeutic regimens (1)vincristine, doxorubicin, and
cyclophosphamide (2) ifosfamide and etoposide
• Surgery
- limb-salvage surgery is preffered
- indications (expendable bone, bone defect able to be
reconstructed with modest loss of function)
• Radiotherapy
- in combination with chemotherapy
- for radiation responsive tumour
MULTIPLE MYELOMA &
BONE METASTASIS
CHIN IE XUAN
BMS15091568
 Multiple Myeloma

• Malignant B cell lymphoproliferative disorder of the bone

marrow with plasma cell predominating

• most common primary malignancy of bone

 Clinical Manifestation

• Fatigue
• Bone pain
• Anemia
• Pathological fracture
• Bleeding
• Spinal cord compression
• Infection
• Hypercalcemia
• Renal failure
 Investigation
• FBC - normal or low
• Serum albumin - normal or low
• ESR / CRP - raised
• SPE - monoclonal band
• Blood film - Rouleaux formation ,
macrocytosis • Serum free light chain assay

• U&E , Cr - renal failure

• Uric acid - normal / raised
• Serum B2 microglubulin > 2.5mg/L
• 24-hr urine electrophoresis - light
• Raised LDH chain excretion

• Serum calcium - normal or raised • Bone marrow aspirate - infiltration

of plasma cells
• Total protein - raised
1) X-ray

• multiple punched out sharply demarcated purely lytic lesion

without any surrounding reactive sclerosis

• lack of reactive bone formation

2) Immunochistochemistry

• +ve for CD56

3) Monoclonal gammopathy
 Metastatic Bone Disease

Cancer that begins in an organ, then spreads to bone

The most common cancers that arise from organs and spread
to bone include:

• Breast, Lung, Thyroid, Kidney ,Prostate

Cancer most commonly spreads to these sites in the skeleton:

• Spine, Pelvis, Ribs, Skull, Upper arm, Long bones of the leg
 Clinical Features

• Pain

• Fracture

• Anemia

• clinically silent (discovered incidentally on X-ray after

pathological fracture)
 Imaging A technetium bone scan
demonstrates extensive bony
metastasis throughout the
skeleton (arrows).

• 1) X-rays.

• 2) computerized tomography (CT)

scan

• 3) magnetic resonance image

(MRI)
 Lab investigation
• Serum alkaline phosphatase - Indirect reflection of
bone destruction because it is a reflection of osteoblastic
response; may not be elevated in purely lytic tumors, such as
plasma cell myelomas; nonspecific because it can also be elevated
in Paget disease, benign insufficiency fractures, endocrine disease,
and others

• Serum protein electrophoresis (SPEP)

• Urinalysis, urine protein electrophoresis (UPEP)

 Treatment
• The most common treatment options for MBD include
radiation and medications to control pain and prevent
further spread of the disease, and surgery to stabilize bone
that is weak or broken.

(Left) This x-ray shows a large defect filled

with bone cement on a thighbone. A plate and
screws have been applied to support the
bone. (Right) In this x-ray, the thighbone is
stabilized with an intramedullary nail and
special screws.
 REFERENCES
• What Is Osteosarcoma?. 2018. What Is Osteosarcoma?. [ONLINE]
Available
at: https://www.cancer.org/cancer/osteosarcoma/about/what-is-
osteosarcoma.html. [Accessed 28 September 2018].
• Osteosarcoma (Conventional) : Bone Tumor Cancer . 2018.
Osteosarcoma (Conventional) : Bone Tumor Cancer . [ONLINE]
Available at: http://www.tumorsurgery.org/tumor-education/bone-
tumors/types-of-bone-tumors/osteosarcoma-conventional.aspx.
[Accessed 01 October 2018].
• Apley and Solomon’s Orthopaedics and Trauma Textbook
• Apley’s and Solomon’s Concise System of Orthopaedics and
Trauma , Fourth edition.
• https://orthoinfo.aaos.org/en/diseases--conditions/giant-cell-tumor-
of-bone/
• https://www.orthobullets.com/pathology/8046/giant-cell-tumor
 References
• https://emedicine.medscape.com/article/9903
78-treatment#d9
• http://www.learningradiology.com/archives2
007/COW%20279-
Ewing%20Sarcoma/ewingscorrect.html
Thank you