Oncology

Question 1

Giant Cell Tumour
1. What is your provisional Dx and differential Dx?
2. How will you stage your Dx and why is this useful
3. How will you further investigate for Dx?
4. What is the likelihood that this lesion is malignant?
5. How will you confirm your diagnosis?
6. If this is a GCT of proximal tibia, what are your principles of treatment?
7. What is the risk of recurrence?
8. If recurrence did occur, what is your management for this patient?

Answer 1

1. GCT. TRO ABC, TOS, browns tumour and infection.
   Older age group - think metastases from RCC and lungs
   Younger age (skeletally immature)- chondroblastoma
2. Campanacci staging
   - based on radiographic appearance
   a) Grade 1 (latent)
   - well defined margin, intraosseous, cortex intact
   b) Grade 2 (active)
   - well-defined margin, cortex expanded and thinned out.
   c) Grade 3 (aggressive)
   - margins indistinct, cortical break, soft tissue extension

Purpose of Staging is
i) to plan for treatment
- Grade 1 and 2: extended currettage, bone graft and bone cement +/- prophylactic internal fixation
- Grade 3: wide excision and reconstruction

ii) to predict prognosis
- the higher grade, the higher the recurrence rate

Question 2

Staging

1. What is staging?
2. Why stage?
3. How do we stage a tumour?
4. What classifications are used to stage a bone & soft tissue tumour?

Answer 2

1. What is staging?
2. Why stage
   - guides diagnostic work up
   - guides treatment strategies for local control
   -guides the need for adjuvant treatment
3. How do we stage a tumour?
   Local staging - MRI of the affected limb
   Systemic staging - CT thorax
4. MSTS/Enneking for bone
   AJCC for soft tissue

Question 3

Malignant Soft Tissue Tumour - upper limb

1. Describe the images as attached.
2. What is your differential diagnosis?
3. How will you investigate and manage this patient?

Answer 3

1. MRI Axial view of the arm, with T1 and T2 weighted images.
   Soft tissue tumour in the medial posterior compartment, compressing/displacing triceps brachii muscles.
   - Well-encapsulated
   - dark on T1, isointense with adjacent muscle
   - bright on T2, relative to surrounding
   - heterogenous on both T1 and T2
   - Plane- beneath fascia
   -adjacent to neurovascular bundle but not involving
2. Soft tissue sarcoma
   Typically dark signal on T1, bright signal on T2
3. Investigation
   Suspect malignant soft tissue, untill proven otherwise
   Systemic staging - CT thorax
   Biopsy

Wide local excision of the STS, send for HPE

Question 4

Benign Soft Tissue Tumour - Lower limb

1. Describe the images as attached.
2. What is your differential diagnosis?
3. How will you investigate and manage this patient?

Answer 4

1.MRI Axial view of the thigh, with T1 and Fat suppressed images.
Homogenous lesion
Beneath fascia, within muscle
Bright on T1 -isointense with subcutaneous fat
on FS- uniform loss of signal, remains isointense with with subcutaneous fat

2. Intramuscular lipoma
3. No further IX required
   Benign - wont metastasize

Marginal excision, send for HPE

Question 5

Malignant Soft Tissue Tumour - upper limb

1. Describe the images as attached.
2. What is your differential diagnosis?
3. How will you investigate and manage this patient?

Answer 5

1.MRI coronal view of the shoulder, with T1 and T2 weighted images.
Soft tissue mass
- overlying the deltoid muscles
- appears to be in subcutaneous plane
- isointense with suncutaneous fat on T1
- with septations
- on FS, some areas demonstrate loss of signal, some areas with persistent high signals

2. Well differentiated liposarcoma
3. Systemic staging - CT thorax, abdomen, pelvis
   - look for lung and retroperitoneal metastases

Wide local excision, send for HPE

Question 6

Metastatic bone lesion

Scenario:
Elderly patient, pain at hip and unable to weight bear after a fall.
Attached is patient’s plain radiograph of the hip.

1. Describe the images as attached.
2. What is your differential diagnosis?
3. How will you investigate and manage this patient?

Answer 6

1. Plain radiograph of the right hip belonging to the elderly patient.
   - Lytic lesions at neck of femur and possible at greater and lesser trochanter
   - Evidence of fracture at femoral neck fracture
   - No fracture at pertrochanteric region
   - Joint space well preserved.
2. Metastatic bone lesion (primary is carcinoma from BLTPK) , Multiple myeloma, Lymphoma, Paget’sdisease
3. Investigations
   a) Further history of current or prev hx of cancer.
   b) Further history on risk of cancer
   female- breast lump
   male- urinary disturbance
   enlargment of thyroid
   smoking hx

c) Examination
- BLTPK
- hepatomegaly, splenomegaly, kidney
- contralateral limb pain

d) Plain radiograph of the right LL from hip joint to knee.

e) Chest xray

f) Bone scan (Technetium - 99)
Skeletal survey - MM, Thyroid CA
g) Bloods
FBC
RP
LFT
Ca, phosphate, ALP
LDH (lymphoma)
urine and serum immunoelectrophoresis (Multiple Myeloma)
Tumour markers
Urinalysis (Renal cell carcinoma)

h) in patients where a primary carcinoma is not identified, obtaining a biopsy is necessary to rule out a primary bone lesion

Management
1. Management of Hypercalcemia
- Blood values, symptoms
- is a medical emergency

Treatment:
a) Hydration to achieve volume expansion
b) Loop diuretics
c) Bisphosphonate

2. In the case of FRACTURE, no need to score Mirrel, as you would need to fix this.
   Aim of fixation
   - reduce pain
   - enable patient to be more independant- sit up, sit on wheel chair, ambulate.
   - easier nursing care.

Management

If not all femur is involved –> Endoprosthesis with cement

If all femur is involved –> Long cephalomedullary with cement

Refer oncology team for post op radiation

Question 6

Metastatic bone lesion

Scenario:
Elderly patient, pain at hip on mobilisation, no previous fall.
Attached is patient’s plain radiograph of the hip.

1. Describe the images as attached.
2. What is your differential diagnosis?
3. How will you investigate and manage this patient?

Answer 6

1. Plain radiograph of the right hip belonging to the elderly patient.
   - multiple lytic lesions at pertrochanteric, wide zone of transition, endosteal scalloping of cortices,
   - no evidence of fracture at femoral neck and pertrochanteric region
   - Joint space well preserved.
2. Metastatic bone lesion (primary is carcinoma from BLTPK) , Multiple myeloma, Lymphoma, Paget’sdisease
3. Investigations
   a) Further history of current or prev hx of cancer.
   b) Further history on risk of cancer
   female- breast lump
   male- urinary disturbance
   enlargment of thyroid
   smoking hx

c) Examination
- BLTPK
- hepatomegaly, splenomegaly, kidney
- contralateral limb pain

d) Plain radiograph of the right LL from hip joint to knee.

e) Chest xray

f) Bone scan (Technetium - 99)
Skeletal survey - MM, Thyroid CA
g) Bloods
FBC
RP
LFT
Ca, phosphate, ALP
LDH (lymphoma)
urine and serum immunoelectrophoresis (Multiple Myeloma)
Tumour markers
Urinalysis (Renal cell carcinoma)

h) in patients where a primary carcinoma is not identified, obtaining a biopsy is necessary to rule out a primary bone lesion

Management
1. Management of Hypercalcemia
- Blood values, symptoms
- is a medical emergency

Treatment:
a) Hydration to achieve volume expansion
b) Loop diuretics
c) Bisphosphonate

2. In the case of NO FRACTURE, score Mirrel
   Trochnteric region (3)
   2/3 (3)
   Lytic (3)
   Moderate (2)
   Total = 11
   Based on Mirel, should be fixed prophylactically to prevent occurence of fracture.
3. Choice of fixation
   Long cephalomedullary nail with cementation

Refer oncology team for post op radiation

Question 7

Metastatic bone lesion

1. Describe the Mirel score.
2. How is the Mirel score used.

Answer 7

1. The Mirel Score
   Mirel staging system is based on 4 characteristics
   a) Site
   1 - UL
   2 - LL
   3 - Trochanteric region

b) Size of lesion (as a fraction of cortical thickess)
1 - <1/3
2 - 1/3 -2/3
3 - > 2/3

c) Nature of lesion
1- Blastic
2 - Mixed
3 - Lytic

d) Pain
1 - Mild
2 - Moderate
3 - Functional

2. Usage of Mirel
   In cases of impending fracture
   Definition: as a ‘lytic’ bony lesion, involving more than ½ the diameter of the bone, greater than 2.5 cm in greatest diameter, or as associated with persistent pain or radiographic progression after radiation.

Based on an overall score, a recommendation for or against prophylactic fixation of a lesion (no fracture yet) is given.

According to Mirels’ recommendation, prophylactic fixation is highly indicated for a lesion with an overall score of 9 or greater.

A lesion with an overall score of 7 or less can be managed using radiotherapy and drugs.

An overall score of 8 presents a clinical dilemma. The probability of fracture is only 15% and Mirels recommended the attending physician use clinical judgment in such cases and consider prophylactic fixation.

Question 8

Biopsy

1. What is biopsy?
2. Describe the types of biopsy.
3. Name lesions that DO NOT NEED biopsy.
4. Name features of lesions that NEED biopsy.
5. What are the principles of biopsy.

Answer 8

1. Biopsy is the final diagnostic procedure, usually performed intralesionally, after imaging, before definitive treatment (chemo/radio/surgical), for purpose of
   - to confirm the diagnosis (type)
   - for histological grading (grade).
   - to determine % of tumour necrosis after neoadjuvant treatment.
2. Types of biopsy
   Open vs Close method
   Close
   - Fine needle
   - Tru Cut
   - Trephine

Open
- Excisional
- Incisional

Non-image guided vs Image-guided

3. DO NOT NEED biopsy

• lesion that has clinicoradiological features of benign characteristics
  Eg.
• Ganglion cyst
• Subcutaneous lipoma
• Non-ossifying fibroma
• Fibrous dysplasia
• Enchondroma
• incidental findings
• stress fracture

4. Features of lesion that NEED biopsy
   All aggressive benign tumours
   All suspected malignant tumours
   - > 5 cm in size
   - Increasing in size in short period.
   - Deep lesion
5. Principles of biopsy
   - Should be performed by the orthopedic oncology surgeon doing the definitive surgery. If IR is doing the biopsy, placement of needle should be as advised by primary surgeon.
   - Go though muscle, avoid intermuscular/neurovascular plane.
   - Along the line of incision of future definitive surgery
   - Use longitudinal incision, avoid transverse incision
   - Do not violate joint
   - in a lesion, target peripherally which has the most undifferentiated cells. Avoid centrally, as more percentage of necrotic/ossified cells. If bone and soft tissue involvement, target soft tissue extra-osseous component as more representative. Target solid, avoid cystic region.

Principles of OPEN BIOPSY (10)

1. Longitudinal incision in line with future resection (expansile nature of tumour)
2. Single compartment
3. Avoid neurovascular bundle/ intermuscular plane - if want limb salvage
4. Biopsy soft tissue component of a bone lesion if present -similar finding, biopsy of the bone will weakened it further
5. Strict homeostasis
6. Drain in line with incision (if cannot achieve hemostasis)
7. Peripheral part of tumour preferred to central, target solid rather than cystic
8. Send also for bateriologic analysis (apart form HPE) for all the biopsied tissue
9. Oval or round shape in a bone has to be made – prevent stress riser
10. Done by surgeon doing definitive surgery.

Question 9

Describe Advantages and Disadvantages of the different techniques of biopsies.
1. Fine needle aspiration/biopsy
2. Core needle biopsy/ Tru-cut biopsy.
3. Incisional biopsy
4. Excisional biopsy

Answer 9

1. Fine needle aspiration/biopsy
   Setting- can be done in clinic under LA, can be done in radiology suite using USG-guided (for soft tissue) or CT-guided (for bone).
2. Core needle biopsy/ Tru-cut biopsy.
   Indication: Superficial or accessible deep extremity lesion that are of sufficient size to allow placement of needle (size > 3 cm) and do not involve major neurovascular structures.

Setting- can be done in clinic under LA, can be done in radiology suite using USG-guided (for soft tissue) or CT-guided/ fluroscopic-guided (for bone).

Technique
- using biopsy needle which is hollow and has cutting mechanism, through which can obtain a cylindrical core of tissue approximately 2mm in diameter, several mm in lengh.
- tru-cut for soft tissue lesion (tru-cut needle)
- core needle for bone lesion (Jamshidi, Islam-hollow trephine type needle)
- need to have 2-3 passes of needle.

Advantages:
- percutaneous stab incision required with LA used.
- obtain more tissue in form of cylindrical core tissue to allow evaluation of pattern of tissue organisation and cellullar features.
- can obtain lesional tissue more rapidly for HPE.
- less costly than hospital-based procedure.
- limited soft tissue contamination
- limited risk as long as biopsy site, needle entry point, needle course are carefully planned.
- easily repeated.
- high diagnostic accuracy -83-96%

Disadvantage:
- limited size of tissue sample obtained- reduce accuracy, increase sampling error, not enough for molecular diagnostic testing.

3. Incisional biopsy
   Technique:
   - incision as small as possible.
   - longutudinal incision, in line with long axis of extremity.
   - shart incision direct to tumour, minimal dissection, avoid crushing with forceps.
   - aim to get peripheral of tumour as most representative.
   -biopsy target soft tissue rather than bone.
   - if no soft tissue component, make a bone window as small as possible, oval with rounded edges (not square to reduce stress riser), seal with bone wax or PMMA.
   - if bone window performed, avoid Codman’s triangle (reactive bone region), irradiated tissue.
   - meticulous haemostasis.
   - careful wound closure.
   - avoid tourniquet use as increase risk of tumour dissemination after released. If need to use, deflate it and secure haemostasis before closure.
   - when using drain, place it at the end of incision, where drain tract can be excised en-block together with tumour later.
4. Excisional biopsy
   for small benign tumours

Setting:
- in OT, under GA/spinal

Advantages
- can obtain larger size of the lesion sample for more extensive histological assessment.

Disadvantages
- risk of improper execution by surgeon.
- risk of tissue contamination.

Question 10

Biopsy

Describe pinciples of Open biopsy.

Answer 10

1. Longitudinal incision in line with future resection (expansile nature of tumour)
2. Single compartment
3. Avoid neurovascular bundle
4. Biopsy soft tissue component of a bone lesion if present
5. Strict homeostasis
6. Drain in line with incision
7. Peripheral part of tumour preferred to central
8. Culture the biopsied tissue
9. Oval or round shape if a hole in a bone has to be made – prevent stress riser

Question 11

A 61-year-old female presents with a 6 month history of pain in the left hip and thigh.

A hip radiograph is shown in Figure A.

Serum protein electrophoresis is normal, and a bone scan shows increased uptake in the left femur only.

A biopsy is taken and shown in Figure B.

What is your differential diagnosis?

Answer 11

Metastatic carcinoma

• Metastatic carcinoma is the most common cause of a destructive bone lesion in older adults.
• Bone is the third most common site of metastasis, behind the lung and liver.
• The pathology slide shows a mixture of glandular cells and bone, representing metastatic gastric cancer.

Not other DDX because:
Osteosarcoma, chondrosarcoma, and primary lymphoma of bone lack the presence of glandular cells on histology.

Osteosarcoma occurs predominately in the metaphysis, and is often associated with periosteal reaction. Patients with multiple myeloma will usually show elevated serum protein electrophoresis levels.

Question 12

Metastatic Bone Tumour

A 70-year-old male presents to your clinic complaining of left hip pain for the past 3 weeks that is made worse with weight bearing. He has a positive cancer history and is status post right nephrectomy. He has been doing well for the past 5 years and recent staging studies show no other evidence of disease.

Radiographs of his left hip and histology of the lesion are provided in figures A and B.

Prior to this, he was an unassisted community ambulator.

1. What is your diagnosis?
2. What is the best treatment option at this time? why?

Answer 12

1. Metastatic renal cell carcinoma (RCC) to the bone
2. Patient would benefit most from a proximal femur replacement in this scenario + pre-op embolisation

Pre-op embolisation
- RCC to the bone (and thyroid) is typically well vascularized and can be associated with substantial intra-operative blood loss; pre-operative embolization should be considered

Mirel scoring > 9: should fix prophylactically
No role for conservative- RCC is radioresistant
Options:
Proximal femur replacement with endoprosthesis (vs long cephalomedullary nail with cement augmentation)
- Due to advances in chemotherapy, patients with RCC are living longer, and incomplete resection of bony metastasis can lead to progression of the disease so the more limited treatment strategies (ex. curettage and ORIF vs. IMN with cement augmentation) may fail in their lifetime. Complete resection is correlated with improvements in overall survival.

Question 13

1. Explain how metastases occurs?
2. What is Batson’s plexus?

Answer 13

1. Mechanism of metastases
   a) Tumor cell intravasation
   - E cadherin cell adhesion molecule (CAM) on tumor cells modulates release from primary tumor focus into bloodstream.
   - Vascular spread to spine - via Batson’s vertebral plexus
   - Vascular spread to extremities - Arterial tree (lung & renal cancer)
   - PDGF promotes tumor migration
   -
   b) Avoidance of immune surveillance
   c) Target tissue localization
   - chemokine ligand 12 (CXCL12) in the stromal cells bone marrow acts as homing chemokine to certain tumor cells and promote targeting of bone.
   - attaches to target organ endothelial layer via integrin cell adhesion molecule (expressed on tumor cells)

d) Extravasation into the target tissue
uses matrix metalloproteinases (MMPs) to invade basement membrane and ECM
e) Induction of angiogenesis
via vascular endothelial growth factor (VEGF) expression
f) genomic instability
g) decreased apoptosis

2. Batson’s vertebral plexus
   - network of valveless venous plexus that connect deep pelvic veins and thoracic veins (draining inferior end of urinary bladder, breast and prostate) to internal vertebral venous plexuses, so this provides a route of metastasis from organs to axial structure including vertebral bodies, pelvis, skull, and proximal limb girdles

-may also allow the spread of infection in a similar manner, eg. pyelonephritis -> spondylodiscitis via this route.

Question 14

Common cancers that metastasize to the bones

Answer 14

Lytic lesions - lung, thyroid, renal
Mixed lesions - breast
Blastic lesions - prostate
Acral metastases - lung, renal, breast

Commonest site
Spine (thoracic spine) > proximal femur > proximal humerus

Commonest site that fracture due to bone mets
Proximal femur

Question 15

A 48-year-old female presents with a posterior ankle mass. She reports discomfort with certain footware. On physical exam percussion of the mass leads to a radiating pain into the foot. Figure A shows a sagittal T1 MRI of the ankle.

1. What is your diagnosis?
2. How would you manage this patient?
3. How to differentiate cause of the lesion?

Answer 15

1. Tibial nerve Schwannoma (Neurilemmoma)
2. Since symptomatic/affecting daily activity, counsel for marginal excision of the lesion.
   - counsel risk of neurological deficit from surgery.
   - if successful removal, risk of recurrence is low.
3. Differentiate neurilemmomma vs neurofibroma
   MRI: schwannomas are located eccentrically in relation to the nerve, showing less Target sign.

HPE: Verocay bodies on histology are a characteristic finding in a neurilemmoma- which are composed of two rows of aligned nuclei in a palisading formation.
Antoni A and Antoni B

Question 16

1. Describe lesion.
2. What is your diagnosis?
3. If patient is symptomatic, what will be your management?

Answer 16

1. Figure B shows saggital and coronal MR imaging of the mass. Figure C shows axial MR imaging.

MR imaging shows isointense signaling relative to skeletal muscle on T1 weighted images and increased, slightly heterogenous signal intensity on T2 weighted images (known as the “Target signs”).
2. Schwannoma (neurilemmoma) of the forearm.
Schwannomas are benign soft tissue tumors that are derived from schwann cells. They usually arise from the periphery of nerves, known as the epineurium.
They most commonly originate in large peripheral nerves of the head, neck, and flexor surfaces of the upper extremities.

3. Since patient is symptomatic, can perform marginal resection alone.
   Enucleation- careful dissection of epineurium and excising the lesion parallel to the nerve fascicles so the lesion may be extruded.
   Delicate enucleation of a neurilemmoma preserves most of the nerve fascicles and causes minimal nerve functional impairment.

Counselling post surgery:
local recurrence rates are low (<1%) and malignant degeneration is extremely rare.

Question 17

How to approach metastatic lesion?

Answer 17

1. Approach metastatic lesion
   a) Determine possible primary.
   If known……
   **Prof. Hazla:
   Mention rule out causes even in known primary

b) Determine if solitary lesion or multiple.
c) Determine prognosis.
d) Determine if surgery is an option; prophylactic fixation, curative or palliative.

If not known- biopsy the bone lesion

If k/c/o CA, and a new lesion appears >2 years after completing treatment for initial CA, assume it is unrelated (not metastatic) & investigate as for new primary tumour.

Question 18

Differentials for permeative lytic lesion in older age group:

Answer 18

Pleomorphic sarcoma of the bone
Multiple myeloma
Metastatic bone disease

Question 19

How to diagnose Multiple Myeloma?

Answer 19

1) Clonal bone marrow plasma cells >10%
2) One or more myeloma-defining events:
- Increased involved/uninvolved serum free light chain ratio (kappa or lambda)
- One or more focal >5mm osteolytic lesions on MRI / CT / XR
- Hypercalcaemia / abnormal kidney function / anaemia
- Raised serum monoclonal protein or urinary monoclonal protein (Bence-Jones protein)

Question 20

Treatment options in skeletal metastases
i) What is the role of pharmacotherapy / chemotherapy in skeletal metastasis?
ii) Role of surgery
iia) indications for surgery in skeletal metastasis.
iib) aims of surgery in skeletal metastasis.

iii) Role of radiotherapy
iv) Role of pre-op embolisation

Answer 20

i) Prevent propagation of metastasis.

iia) Surgery indication
a) Preventive: Fracture/impending fracture
b) Palliative: Alleviation of pain (no effect on disease progression or patient survival)
c) Curative: Resection of solitary met.
** Cancers for which there is role of resection of solitary met –> Thyroid, renal

iib) Aims of surgery
1) Local tumour control
2) Immediate structural stability
- pathological bone will not heal normally
- cemented implants, no bone graft
3) Immediate weight-bearing
- restoration of normal function ASAP
4) Palliative
- pain relief, nursing care

iii) Radiotherapy
Adjuvant radiotherapy within 2/52 (once wound healed) to 3/12 post-fixation in order to prevent local disease progression
–> prolong survivability of implant in an underlying pathological bone.

iv) Pre-op embolisation: Liver, thyroid, renal

Question 21

Describe margins in resections.

Answer 21

1) Intralesional
2) Marginal
3) Wide resection
4) Radical

Question 22

Wide resection: Recommended cuff of normal tissue.

Answer 22

5cm for cure
2cm adequate
<1cm - considered wide still (since cuff of normal tissue present), but inadequate

Question 23

Criteria for resection of pulmonary metastases:

Answer 23

1) No disease at the site of the primary tumour (recurrence)
2) No metastases outside the lungs
3) No non-resectable pulmonary nodules
4) No non-surgical alternative for cure
5) No evidence that the patient cannot tolerate the proposed surgical therapy

Question 24

Limb salvage surgery: Criteria

Answer 24

Limb salvage recommended only if:
(i) No compromise of adequate oncologic margins
(ii) Salvaged limb provides function equal or superior to prosthetic limb after amputation.

Question 25

Limb salvage surgery: Describe BIOLOGICAL options for limb-salvage reconstruction, pros & cons.

Answer 25

A) Biological

1) Bone transport, eg. Ilizarov
- long time, immunocompromised patients susceptible to infection, time to form & quality of regenerate bone unpredictable because of adjuvant therapies

2) Autologous bone graft
- Non-vascularised, vascularised

Pros
- Cheaper, more biological, highest osteoconductive/inductive/genic potential, lowest risk for disease transmission, immunological response

Cons
- Donor site morbidity, restricted availability
- Conventional fibula graft unable to provide mobile articulating surface -> unability to move joint
- Structurally not strong enough to withstand loading of large defects in lower extremity -> prone to fractures
- Usually combined with allograft

• Sterilising patient’s own bone: autoclaving, microwaving, pasteurising, liquid nitrogen (cryotherapy), radiotherapy *(pasteurisation best)

Pros
- cheap, size-matched
- no need to procure allograft, no need to worry about disease transmission, immunological response
- anatomical re-attachment of soft tissue, higher incidence of incorporation compared to allograft

Cons
- time-consuming, structurally not strong enough -> need to augment with cement, autograft
- local recurrence can occur

3) Allograft
- Usually at diaphysis
- can be osteoarticular - total condylar/hemicondylar

Pros
- More accessible, larger sizes available.
- can be matched to the size of the resected bone.
- has possibility of supporting mechanical loads.
- allow attachment of host ligaments and muscles to the allografts.
- may be progressively incorporated by the host.

Cons
- Disease transmission & immune rejection risks
- bone resorption (functions more as spacer: only small percentage becomes revascularised, remainder remains necrotic)
- risk of infection
- non-union/ delayed union
- late fractures - strenght and elastic modulus of graft affected due to processing techniques.
- Allograft usually used with structural support: filled with bone cement or vascularised autograft.

Osteoarticular - total condylar/hemicondylar
Advantages:
- prohibiting need to sacrifice the other side of the joint.
- replace articular surface for which prostheses are not readily available such as distal tibia or distal radius.
- availability of soft tissues on allograft allows attachment of host tendons or ligaments.

Complication:
Bone graft fractures and resorption
Cartilage degeneration
Joint instability
Delayed union or non-union

Question 26

Limb salvage surgery: Describe NON-BIOLOGICAL options for limb-salvage reconstruction, pros & cons.

Answer 26

II Non-biological

4) Megaprosthesis

Pros
- Spans gap, allows movement of joint
- Provides mobility and stability
- Immediate return to function
- Not affected by on-going chemotherapy/radiotherapy
- Modular implants available, expandable implants

Cons
- Prone to fatigue failure, loosening (infective or aseptic from wear debris)
- Infection
- Lack biological anchorage for soft tissue
(Allograft prosthesis composite attempts to restore bone stock & provide more biological means of anchorage for tendon, muscle insertions.)

III

5) Rotationplasty

Pros
- no phantom pain
- ankle becomes knee, foot becomes useful attachment for below-knee prosthesis
- can be used even after extensive resection

Cons
- cosmetically unacceptable for some

Question 27

What factors need to be taken into consideration in deciding which method of limb salvage?

Answer 27

1) Tumour factors
- Diagnosis
- Site & extent of tumour

2) Patient factors
- Age
- Socio-economic
- Expectations

3) Surgeon factors
- Expertise & infrastructure

Question 28

What are the goals in Limb Salvage Surgery?

Answer 28

Goal:
1. Adequate margin (wide resection of local tumor, ie: en bloc)
2. Preserve function with early return to function
3. LR rate not greater than amputation
4. Not interrupt adjuvant therapy, eg chemotx or RT
5. Good skeletal stability
6. Low incidence of local complication
7. Optimizing aesthetic outcome

Question 29

Contraindication to Limb Salvage Surgery?

Answer 29

Contraindication
1. Adequate residual function not achievable
2. Inadeq oncological clearance
3. Poor expected survival
4. Poorly placed biopsy
5. Major NV
6. Infection / tumor fungation
7. Pathological fracture

Question 30

1. What is Limb Salvage Surgery?
2. What are the options of LSS?

Answer 30

1. Surgical procedures to accomplish removal of a malignant tumour

AND

reconstruction of the limb with acceptable
Oncologic, functional and cosmetic result.

2. Options
   Non-biological
   Biological
   Combination
   Modified amputation

Question 31

What is ENDOPROSTHESIS?
Describe this method of LSS.

Answer 31

Gold standard for LSS in the skeletally mature patients.

Advantages:
- Spans gap, allows movement of joint
- Provides mobility and stability
- Immediate return to function
- Not affected by on-going chemotherapy/radiotherapy
- Modular implants available, expandable implants

Cons
- Prone to fatigue failure, loosening (infective or aseptic from wear debris)
- Infection
- Lack biological anchorage for soft tissue
(Allograft prosthesis composite attempts to restore bone stock & provide more biological means of anchorage for tendon, muscle insertions.)

15-20 year implant survival 51 - 38 %
Good early functional outcome
Long term outcome unsatisfactory
Cannot fully adresss the issue of limb lenght discrepancy in children

Question 32

1. Name types of Biological reconstruction.
2. What are the absolute and relative indications for them?

Answer 32

1. Types
   - Autograft
   - Allograft
   - Recycling autograft (Tumour-bearing bone)
   - Allograft-prosthetic composite
   - Bone transport distraction osteogenesis
   - Arthrodesis (using autograft/allograft)
   - Bone cement spacer & induced membrane technique (Masquelet technique)
2. Indication
   Absolute indications
   - Contained defect
   - small bony defect
   - no implant available except for ‘custome-made prosthesis’ eg talus, calcaneum
   - ligament reconstruction for joint stability eg. distal ulnar resection

Relative indications
- Multiple revisions - eg infected endoprosthesis
- Good long-term results compared with endoprosthesis - eg distal radius, distal tibia
- Soft tissue defect
- Benign tumour
- Upper limb

Question 33

Name an autograft commonly used in Biological reconstruction.
Describe.

Answer 33

Autograft - fibular graft

Options- vascularised & non-vascularised fibular autograft.

Indication- to fill defect following resection of long bone diaphyseal sarcoma.

a) Free vascularised fibular graft (FVFG)
Feature:
- fibular graft is accompanied by peroneal artery vascular pedicle and its periosteal branches.
- Distal ankle’s lateral malleolus is fixed to distal tibia to maintain stability.

Indication
-defect also need for concurrent osteo-myocutaneous flap.
- defect at anatomical sites with limited soft tissue cover eg metatarsal
- defect is long segment.
- can be used in combination with allograft/recycling autograft.
- can transfer with epiphyseal for growth.

Contraindication:
- not suitable for short survival
- metastatic bone disease

Advantages:
- does not undergo necrosis
- revascularisation occurs from its feeding vessels and from surrounding vascular bed.

Disadvantages:
- end up with prolonged surgery
- requirees advanced technique - microsurgery
- infection ‘chemotherapy’
- risk of wound complication
- donor morbidity
- slow rehabilitation - compared to endoprosthesis, as need to wait for bone incorporation.
- occurrence of junctional non-union.
- slow incorporation

Question 34

What is recycling autograft?

Answer 34

Involves sterilisation process via
autoclaving/ pasteurization, extracorporeal irradiation, microwave, liquid nitrogen, immersing in alcohol
** Pasteurization has the best overall outcomes because of its osteocytes preservation and bone marrow cellularity.
** Both irradiation & pasteurization techniques have more favourable outcome in terms of bony union, compared to autoclaving.
(radiographic & histopathological evaluations).

for purpose of
- eradicating tumour cells
- to maintain the biological and structural properties of bone graft

Advantages:
- biological reconstruction with precise anatomical fit.
- no donor site morbidity
- no risk of disease transmission
- avoidance of immunological reaction
- avoidance of complication of using prosthesis
- cheaper options vs allograft from bone bank
- potential preservation of collagenous matrix and other intrinsic proteins after certain sterilisation method.

Disadvantages:
- mechanically weak & brittle (depending on sterilization process) –> delayed union/non-union, fracture.
- potential risk of local recurrence due to tumour cell survival within the recycled autograft.

Question 35

What is the role of Distraction Osteogenesis in LSS for bone sarcomas?

Answer 35

Advantages:
- beneficial for patient with good long-term prognosis.
- good option for growing child.

Disadvantages:
- time consuming
- requires patient’s cooperation
- pin tract infection
-delayed consolidation
-union problem at docking site
-malalignment in large bone defects

Question 36

Name the cell subpopulation types in tumours

Answer 36

3 types
1) Cell that are non-dividing and are terminally differentiated
2) Cells that are continuingly proliferating.
3) Cells that are resting but may be recruited into cell cycle

Question 37

1.What is chemotherapy? What are the modes of chemotherapy?
2.What is the mechanism in chemotherapy?

Answer 37

1. Chemotherapy is the use of drugs, given into vein or taken by mouth, to destroy cancer cells but has systemic effects.

Modes:
a) Primary chemotherapy
- used as sole anti cancer treatment in highly sensitive tumour types
- eg CHOP for non hodgkins lymphoma

b) Adjuvant chemotherapy
- given after surgery to “ mop up” microscopic residual disease.
-eg Adriamycin, Cyclophosphamide for breast CA.

c) Neo-adjuvant chemotherapy
- given before surgery to shrink tumour and increase chance of successful resection
- eg Adriamycin, Ifosfamide for Osteosarcoma

d) Concurrent chemotherapy
- given simultaneously to radiation to increase sensitivity of cancer cells to radiation
Eg. Cisplatin, 5-Florouracil and XRT for head and neck tumor.

2 classes of chemotherapy
- cytotoxic agents - induces apoptosis
- targeted therapies - target specific proteins over-expressed in cancer cells

2. Mechanism
   Systemic chemotherapy is for disseminated malignant disease and may require multiple cycles to cause

• Damage to DNA of cancer cells
• Inhibit syntheses of new DNA strands, to stop cell from replication and subsequently tumour growth.
• Stop mitotic process of a cell.

So targets fast growing cells

Question 38

1. What is tumour necrosis rate? What does it mean?
2. Name chemosensitive and chemoresistant tumours.
3. Side effects of chemotherapy.
4. Monitoring & management of side effects from chemotherapy

Answer 38

1. Tumour necrosis
   >98% necrosis following chemotherapy- good prognosis
2. Chemosensitivity
   Chemosensitive - synovial sarcoma, myxoid/round cell sarcoma
   Moderately chemosensitive - pleomorphic sarcoma

Relatively chemo-insensitive - MPNST, clear cell sarcoma, dedifferentiated liposarcoma
Chemo-insensitive - chondrosarcoma

3. Side effects
   - myelosuppression
   - nausea and vomiting
   - pulmonary fibrosis
   - alopecia
   -sterility
4. Monitoring & management of complications:
   1) Pancytopaenia - FBC, granulocyte colony stimulating factor for neutropaenia
   2) Peripheral neuropathy - early detection & dose modification
   3) Nephro/hepatotoxicity - RP / LFT, adequate hydration
   4) Ototoxicity - audiometry
   5) Cardiotoxicity - echocardiogram

Question 39

Describe Tumour Kinetics in relation to chemotherapy.

Answer 39

Growth pattern and response to chemotherapy can be described by 2 hypotheses
i) Log Kill Hypothesis
ii) Norton Simon Gompertzian Hypothesis

i) Log Kill Hypothesis
-stages that a given dose of chemo kills the same fraction of tumour cells regardless of the size of tumour at the time of treatment
e.g. one dose of drug leads to cytoreduction from 10^6 to 10^4, in the same way that one dose at 10^4 to 10^2 cell volume.
- however this model does not accurately represent clinical reality/ does not completely predict or explain tumour cytogenetics because
* cure is rare for patients with advanced cancer
* many patients with early-stage cancer recur despite treatment.

ii) Norton-Simon hypothesis
- rate of cancer cell death in response to treatment is directly proportional to tumour growth rate/doubling time at the time of treatment.
- chemo sensitive to actively dividing cells.
- this model says log-kill is not constant but instead it is proportional to relative growth rate.
- predicts that smaller tumour experience greater log-kill because of their rapid growth rate, compared to larger tumours.
- hence a kinetic advantage to treatment when tumour volume is small in post op setting.

Question 40

Explain the Gompertzian Growth Model graft in relation to soft tissue tumor and chemotherapy treatment.

Answer 40

In this growth curve which exhibits a sigmoid shape, tumour doubling time varies with tumour size
- most rapid growth when small –> first order growth
- slow growth when tumour is large –> small growth rate, small growth fraction
* as based on cell loss, tumour blood and oxygen supply.

(1) Untreated tumour burden
(2) Infrequent treatment with late start
* prolongs survival but doesnt cure

(3) More intensive and frequent with earlier start
* more succesful
* Kill rate > growth rate

(4) Early surgical removal decreases tumour burden
* Chemotherapy removes secondary tumour with shorter duration

Question 41

Young patient < 15 years old presents with pain at the knee. Radiograph is as shown. What are you differential diagnosis?

Answer 41

Destructive lesion in young patient
- Eosinophilic granuloma
- Osteomyelitis
- Osteosarcoma
- Ewing’s sarcoma
- Desmoplastic fibroma
-Lymphoma
-Leukaemia

Question 42

Young patient < 15 years old resents with pain at the leg. Radiograph is as shown. What are you differential diagnosis?

Answer 42

Multiple lesions in young patients
- lymphoma
- leukaemia
- fibrous dysplasia
- enchondroma/Olliers/Maffucci’s
- osteochondroma/MHE
- non-ossifying fibroma
- Paget’s
- hemangioendothelioma

Question 43

A 5-year-old child presents with skin lesions and a limp. He has met all developmental milestones accordingly but his parents have noticed he has recently stopped gaining weight. Clinical photograph of his skin lesion, radiograph of his left hip, and histology slide representative of his hip lesion are shown in Figures A, B.

1. What is the most likely diagnosis?
2. How to confirm diagnosis?
3. How to manage this?
4. What might you find if surgery was done and bone was sent for HPE.

Answer 43

1. Eosinophilic granuloma
2. Rule out HSC
   - Examination
   * for chest or abdomimal pain.
   * spine kyphosis

• Skull xray - no evidence of multiple punched out lesion
  -spine xray - vertebra plana

3. Management
   Eosinophilic granuloma is a benign neoplasm of histiocytes which is self-limiting.

1st line - Conservative treatment with crutches, observe with repeat radiographs in 6 weeks.

2nd line - Worsening pain and further destruction of the cortical bone would be indications for radiation therapy or curettage and grafting/cementation to prevent pathologic fracture.

4. Pathognomonic findings for eosinophilic granuloma include coffee bean indented nuclei in Langerhans cells (blue arrow in Illustration A) and tennis-racket shaped Bierbeck granules within the Langerhans cell (shown on electron microscopy in Illustration B).

Question 44

A 14-year-old child is referred to your office for evaluation of a tibia lesion found incidentally after a minor ankle injury. A radiograph of the child’s ankle is shown in Figure A.

1. What is your PDx?
2. What other DDX?
3. How will you manage this patient?
4. As you follow up this child, how may this lesion change with time?
5. What is an associated syndrome with this lesion? How is its presentation?

Answer 44

1. Non-ossifying fibroma
   - classic eccentric lesion at the metaphysis, sclerotic margin, ‘bubbly’ with a scalloping appearance, subtle corticle expansion noted.

• commonly found incidentally.
• patient is painless.

2. DDX
   Aneurysmal bone cyst
   Unicameral bone cyst
3. Management
   Since asymptomatic, routine follow up of lesion; 6 and12 monthly then yearly with plain radiograph untill lesion reossified.
4. As child approaches skeletal maturity
   - lesion will become more sclerotic at its border.
   - lesion will resolve spontaneously.
   - lesion may appear to have migrated to diaphyseal as child’s long bone elongates with time.

• if involve > 50% of cortex and the child experiences any trauma to the affected limb, stress fracture may occur –> casting

5. Associated with Jaffe- Campanacci syndrome

will also have
cafe-au-lait spots, mental retardation, and cardiac, optholmalgic or gonadal abnormalities.

Question 45

Question 46

Question 47

1. Describe this lesion.
2. What are your differential diagnosis?
3. What might histological slides show?
4. What is your management?

Answer 47

1. Lytic, expansile lesion at meta-disphyseal region of metatarsal, with narrow zone of transition, septations within lesion.
2. Aneurysmal bone cyst of the metatarsal.
3. Lakes of blood without epithelial cell linings.
   May have benign giant cells and spindle cells.
4. If patient has pain, do curettage, bone grafting.

Question 48

What are the benign bone tumour that are
A) Commonly treated with intralesional Curettage and bone grafting?
B) Occasionally treated with intralesional Curettage and bone grafting?

Answer 48

A. giant cell tumor, chondroblastoma, chondromyxoid fibroma, and osteoblastoma

B. unicameral bone cyst (UBC), enchondroma, and nonossifying fibroma (NOF)

Question 49

1. Describe this lesion.
2. Ix to help with diagnosis?
3. Management if ABC.

Answer 49

1. This is an x-ray of the pelvis demonstrating a multiloculated radiolucent lesion in the left iliac wing.
2. MRI - fluid-fluid levels
3. If painful, do extended curettage with adjuvants such as phenol, argon, liquid nitrogen, high speed burr, followed by bone grafting.

Question 50

Surgical margins

1. Define “surgical margin”.
2. Why important?
3. How to assess?

Answer 50

1. Tissue plane through which dissection is done in relation to the tumour & the actual/potential tumour tissue which could have been left behind.
2. Important
   a) to determine the effectiveness of surgical excision in achieving local control of disease
   b) chances of local recurrence.
   c) need for post op adjuvant treatment - radiotherapy
3. Assessment can be done
   a) Pre operative - MRI- assess local tumour extension and relation to relevant local anatomy.
   b) Intra operative- gross margin determination by surgeon, if questionable can do frozen section
   c) Post operative- HPE analysis of the margins if clear or involved.

Question 51

Sarcoma

1. What is origin of sarcoma?
2. Describe biological behavior of sarcoma.
3. What are the components of reactive zone?
4. What is pseudocapsule?
5. What are the difference between reactive zones of low and high grade sarcomas?
6. What are satellite lesions?
7. What are skip lesions?

Answer 51

1. Sarcomas originate primarily from mesenchymal cells from mesodermal embryonic layer.
2. Biological behaviour - grow centrifugally (from inside to outside)
   - as it grows from side to outside direction, the normal connective tissue surrounding the tumour is compressed and forms capsule whilst there is also fibrovascular zone of reactive tissue with variable inflammatory component from interaction with the surrounding normal tissue (normal tissue reacting towards the growth of sarcoma).
3. proliferating mesenchymal cells (least immature cells, varies from low/intermediate/high grade), neovascularisation and inflammatory cells.
4. Pseudocapsule: reactive zone + remnants of capsule (after having been breeched by sarcoma)
5. Reactive zone features
   Low grade sarcoma - does not grow outside the reactive zone
   High grade sarcoma - will destroy capsule and reactive zones are poorly defined.
6. Satellite lesions- tumor foci not in continuity with and main tumour mass and forms within the pseudocapsule
7. Skip lesions - tumor foci not in continuity with and main tumour mass that have break through pseudocapsule to form metastases within the same anatomic compartment in which the lesion is located.

Question 52

Surgical margins

Describe Enneking classification of surgical margins

Answer 52

Enneking et al, 1983

describes surgical margin into

a) Intralesional
- lesion removed from within the pseudocapsule of the gross tumour.
- margin has gross tumour
- leaves behind portion of the gross tumour, the reactive zones that has satelite lesions and skip lesions.

b) Marginal
- lesion removed en bloc
- plane of dissection is extracapsular (either between pseudocapsule and reactive zone or within reactive zone.
- margin has reactive tissue
- remaining tissue are portions of reactive zone containing satellite and skip lesions.

c) Wide
- lesion has been removed en bloc, and the plane of dissection has been peripheral to the
reactive zone through normal tissue but has taken place within the compartment of origin.
- No natural barrier is between the lesion and the margin.
- Left in the wound are the skips in the remaining normal intracompartmental tissues.
- If the lesion is extracompartmental, the dissection takes place in normal tissue beyond the reactive
zone but between the reactive zone and the boundaries of the adjacent compartment.

d) Radical
- The lesion and the entire compartment(s) which it involved have been removed en bloc.
- The plane of dissection has taken place peripheral to the boundaries of the compartment in the
transverse sense and proximal and distal to the longitudinal extent of the compartment.
There must be a natural barrier(s) between the margin of the wound and the lesion in all
dimensions.
- If a lesion is extracompartmental, a radical margin is achieved only when the dissection takes
place peripheral to the barrier of the adjacent compartment(s) in the tranverse sense and proximal
and distal to the longitudinal extent of the adjacent compartment(s)
- No residual tumour is left

Question 53

Surgical margins

Describe the new classification system used for surgical margins.

Answer 53

Kawaguchi et al 2005 (Japanese Ortho Association)

Surgical margin is evaluated according to the distance of the margin from the tumour’s reactive zone,

and consequently is classifiable into the
4 categories of curative, wide, marginal, or intralesional margin.

a) curative margin
- is defined as a margin 5 cm or more outside the reactive zone.
- specimen has normal cuff of tissue 5 cm or more.

b) wide margin
- margin 4 cm to 1 cm outside the reactive zone.
- inadequate: normal cuff of tissue 1 cm
- adequate: normal cuff of tissue > 1 to 4 cm.

c) marginal margin
- is a margin passing through the pericapsular reactive zone

d) intralesional margin
- is a margin passing through the tumor parenchyma

Question 54

Surgical margins

1. What is
   A barrier
   Thick barrier
   Thin barrier
2. Why is knowing this important?

Answer 54

1. Barriers
   Definition: Any tissue that has any resistance against tumor invasion.

• include muscle fascia, joint capsule, tendon,
  tendon sheath, epineurium, vascular sheath, cartilage, pleura, and peritoneum

Thick barrier:
- physically strong membranous tissue with a white tendinous luster, an iliotibial band, presacral fascia, joint capsule, periosteum of infant/young child.
- thick barrier = 3 cm thickness of normal tissue
- joint cartilage = 5 cm

Thin barrier:
- weaker membranous tissue of muscle fascia, periosteum of an adult, vessel sheath, and epineurium
- thin barrier = 2 cm thickness of normal tissue

However, when tumour has adherence to
membranous barrier, the outer surface of the barrier remains tumour free, as such the barrier is evaluated by deducting 1 cm from the original value.

eg
if tumour adheres to thick barrier, it is evaluated as 2 cm.
if tumour adheres to think barrier, it is evaluated as 1 cm.

2. Importance of knowing barrier effects
   - surgery can be done at sites where barrier exist by using less margin than true physical distance.
   - can perform limb salvage surgery without affecting important neurovascular structures.

Question 55

Surgical margins

What are the recommended surgical margins to achieve safe margins
a) high grade sarcoma
b) low grade sarcoma
c) Recurrent sarcomas

If insufficient margins, what is next management?

Answer 55

1. Safety margins

a) High grade sarcoma
o primarily treated with surgery or secondarily by surgery but inadequate or ineffective preoperative treatment (eg Neoadjuvant chemo)
▪ > 3 cm wide margin is necessary

o Effective preoperative assessment (imaging, physical findings)
▪ 2 cm wide margin is allowed

b) Low grade sarcoma
o Adequate wide margin is essential - 1 cm
o Partial marginal margins are acceptable at
sites where barriers exist (periosteum, vessel sheath, muscle fascia)

c) Recurrent sarcoma in a low-grade or high-grade
sarcoma
o A curative procedure is necessary

2. Insufficient margin
   o Radiotherapy should be used regardless of
   the tumour grade

Question 56

Surgical margins

What are the margins for metastatic bone disease?

Answer 56

1. Curative surgery
   ▪ Solitary mets from the primary tumor eg breast,
   - the lesion is treated as if it is a primary bone sarcoma ( wide excision )
2. Palliative surgery
   ▪ Metastatic lesions are treated by an intralesional procedure

Question 57

Imaging

What is FDG- PET CT scan?

Answer 57

FDG-PET CT
18 - fluorodeoxyglucose (FDG)-positron emission tomography (PET)- CT
FDG- detects lesions with enhanced glucose metabolism
CT can detect osteoblastic lesions without enhanced glucose metabolism

Usage
- assisting diagnosis
- staging of patients with newly diagnosed malignancy
- restaging following therapy and surveillance- for any recurrence or mets - evaluate tumour activity based on glucose uptake

Question 58

Imaging

Role of CT in bone tumour?

Answer 58

Local lesion:
- to assess extent of bone destruction
- to detect occult/pathological fractures
- if with contrast, to evaluate vessels and enhance soft tissue involvement

Systemic:
- to assess for pulmonary metastasis

Question 59

Imaging

Role of MRI in bone tumour?

Answer 59

Local lesion for local staging

-Assess location of tumour ie. which compartment, which muscle involved
- Assess relation to surrounding structure ie neurovascular bundle
- Assess extend of involvement for safe/adequate resection eg intramedullary extension, soft tissue involvement
- Assess for skip lesions

Question 60

Imaging

Role of plain radiograph in bone tumour?

Answer 60

Local lesion:

Can diagnose 80% of tumour cases
Can rule out fracture/impending fracture
Lesions at extremity appear early than spine and pelvic bone lesion

Question 61

Imaging

What are your sequence used for describing plain radiograph with bone lesion?

Answer 61

Name, date
Type of Xray - eg AP and Lateral view of right/left tibia and fibular, with proximal and distal joint involved.
Age of patient - skeletally mature or immature
Describe from inside out
- bony lesion location; epiphysis, metaphyseal, diaphyseal
- centrally, eccentrically
- cortical, juxtacortical
- transition zone - narrow or wide
- blastic/lytic
-matrix - calcification, mineralisation
- cortical destruction
- periosteal reaction
- soft tissue swelling- with/without calcification
- presence of skip lesion

Question 62

Bone sarcoma

Key features to differentiate malignant and benign lesion

Answer 62

a. Age

b. Zone of transition

i) Narrow zone
- sharply defined margin
- slow growing
- benign

ii) Wide zone
- ill defined margine
- signs of aggressive tumour
- may mimic infection and eosinophilic granuloma/histiocytosis

Question 63

GCT

1. Describe plain radiograph.
2. What is your diagnosis and differentials?

Answer 63

1. Describe
   - plain radiograph of knee joint in AP and lateral projection belonging to a skeletally mature patient.
   -Lytic lesion at metaphyses extending to epiphyses and subchondral region.
   - Narrow zone of transition
   - Cortical thinning but no destruction.
   - no periosteal reaction or soft tissue extension
2. GCT
   DDX: ABC, Telangiectatic osteosarcoma, infection

Question 64

GCT

1. Describe plain radiograph.
2. What is your diagnosis and differentials?
3. How will you obtain bone samples for diagnosis?
4. How will you manage this condition?

Answer 64

1. Describe
   - plain radiograph of wrist joint in AP and lateral projection belonging to a skeletally mature patient.
   -Lytic lesion at metaphyses extending to epiphyses and subchondral region.
   - Narrow zone of transition
   - Cortical thinning but no destruction.
   - no periosteal reaction or soft tissue extension
   - no DRUJ dysruption, ulnar and carpal bones are spared.
2. GCT of the radius
   DDx: infection, osteosarcoma (rare)
3. Biopsy
   via the radial styloid because
   - it is the shortest route
   - can avoid neurovascular bundle

all to avoid contamination and dissemination of disease

4. Management
   - extended currettage with high speed burr (wide resection)
   - adjuvant - chemical
   -bone grafting and PMMA for reconstruction
   - can use autologous fibula graft/ allograft

Question 65

GCT

1. What are the non-operative treatment options for GCT? How does this help with management of GCT?
2. What are the indications for non-operative mx of GCT?
3. What is inoperable GCT?
4. Disadvantages of non-operative treatment options?

Answer 65

1. Non-operative management
   A) Systemic
   a) Denosumab
   - is Human monoclonal antibody that acts as a RANK ligand inhibitor, by binding to RANK ligand receptors and inhibiting activation, so inhibit osteoclastic activity of tumour cells.
   - indirect action
   - inhibit osteoclast function/activity

b) Bisphosphonate
- Pyrophosphate analoque
- direct inhibition of mevalonate pathway
- inhibit osteoclast function/activity
- inihibit osteoclast survival

Can be used pre-operatively or on its own as totally conservative management

Pre-operative usage to promote consolidation and marginalization of tumour
- to facilitate surgery, from resection to curettage
- allow manipulation
- prevent fracture or collapse
- reduce blood loss
- prevent contamination

(Advantage to surgeon)

Pre-operatively: 3 doses 120mg day 1, 8, 15, 29;
surgery within 2-3/52 after last dose (otherwise layer of new bone will be too thick)

1) Sclerose lesion
- for ease of handling -> (i) facilitates intralesional curettage, (ii) prevent spillage / tumour contamination, (iii) in cases of tumour with cortical breakage or soft tissue extension, to solidify tumour prior to wide resection (downgrades from Campanacci III to lesser grade; does NOT reduce tumour size)

2) Reduces vascularity of GCT - less blood loss intra-op.

(Advantage to patient)

3) Prevents disease progression in cases of lung mets.
4) Unresectable disease
Improve Quality of Life by
- Reducing pain
- Improvement neurology (return of bladder and bowel control for GCT sacrum)
- Promote regression of tumour
- Prevent progression of lung metastasis

**No role post-op. to prevent local recurrence.

B) Radiotherapy
- inoperable cases
- 5 year local control up to 80%
- risk of sarcoma transfoermation 3-11%

2. Indications for non-operative mx.
   i) Recurrent disease
   ii) metastatic disease
   iii) inoperable site
3. Inoperable GCT
   GCT sacrum
   GCT spine
4. Disadvantages
   Denosumab & Bisphosphonate
   - osteonecrosis of jaw, atypical femoral fractures

Radiotherapy
risk of sarcoma transformation

Question 66

Imaging

What is the role of Technetium-labeled bone scan?

Answer 66

• to determine monostotic versus polyostotic lesions
• to identify occult bone involvement.
• detects osteoblastic activity - hot spots
• less sensitive in cases of lytic lesions eg multiple myeloma, thyroid carcinoma.

Question 67

Diagnosis

Multiple lytic lesions in child < 5 years old.
What are your DDX?

Answer 67

Metastatic neuroblastoma/ Wilms tumour
Langerhans cell histiocytosis
Fibrous dysplasia
Osteomyelitis

Question 68

Diagnosis

Name tumours based on anatomical location in long bones

i) Epiphyseal

ii) Metaphyseal

iii) Diaphyseal

Answer 68

i) Epiphyseal (PG CAT)
- PVNS
-Giant cell tumour
- Chondroblastoma/ Clear cell chondrosarcoma
- ABC
-TB and other pyogenic infection

ii) Metaphyseal
-Osteosarcoma
-Chondrosarcoma
-Metastatic disease
- UBC
- NOF

iii) Diaphyseal
A - Adamantinoma
E - Eosinophilic granuloma
I - Infection
O - Osteoid osteoma/osteoblastoma
U - Ewing sarcoma
Y -MYeloma, lYmphoma, fibrous dYsplasia
M - metastases

Question 69

Diagnosis

Plain radiograph of a bone lesion.
Using Enneking’s 4 questions, how will you reach a diagnosis?

Answer 69

1. Location - where is it- epiphyseal, metaphyseal, diaphyseal
   2.Tumour-bone interaction
2. Bone-tumour interaction
3. Matrix - what is the tumour producing - bone, cartilage?

Question 70

Diagnosis

Plain radiograph of tumour with cortex involvement at metaphyseal.

Answer 70

• Non-ossifying fibroma
• Chondromyxoid fibroma
• Osteochondroma

Question 71

Diagnosis

Plain radiograph of tumour with intramedullary involvement at metaphyseal

Answer 71

• Osteosarcoma
• Chondrosarcoma
• Enchondroma

Question 72

Diagnosis

Plain radiograph of tumour with intramedullary involvement at diaphyseal.

Answer 72

• Ewing sarcoma
• Langerhans cell histiocytosis
• Multiple myeloma

Question 73

Diagnosis

Plain radiograph of tumour with cortex involvement at metaphyseal

Answer 73

• Osteoid osteoma
• Osteofibrous dysplasia
• Adamantinoma

Question 74

Lymph node

Sarcomas with Lymph Node involvement

Answer 74

SCARE:
Synovial sarcoma
Clear cell sarcoma
Angiosarcoma
Rhabdomyosarcoma,
Epithelioid sarcoma

Question 75

Metastatic disease

What are your goals in treatment of metastatic bone lesion?

Answer 75

Goals

1. Maximize ability for immediate mobilization and weight bearing
2. protect the entire bone in setting of systemic and metastases disease
3. optimise implant choice in the context of patient’s overall prognosis.

Question 76

Metastatic disease

Patient with breast CA with only mets to proximal femur with fracture. No mets to other organs.

What is your management
a) for the femur fracture?
b) contralateral side that has lytic lesion?

Answer 76

a) Pathological fracture management.
Breast CA is good prognosis

Treatment is curative intent

Treatment type - resect and replacement with endoprosthesis/ bipolar hemi athroplasty with long stem, cemented.

b) Lytic lesion at contralateral side, no fracture?
- Score Mirrel’s
- > 8: to fix

Question 77

Metastatic disease

Patient with lung CA with only mets to proximal femur with fracture. No mets to other organs.

What is your management
a) for the femur fracture?
b) contralateral side that has lytic lesion?

Answer 77

a) Pathological fracture management

Lung CA is poor prognosis

Treatment is palliative intent.
- to enable patient to mobilise prior to disease progression.

Treatment type - Not for endoprosthesis
- Use long stem bipolar hemi + cement

Question 78

Chemotherapy

1. What is chemotherapy?
2. What are the benefits of

i) Neoadjuvant chemotherapy

ii) Adjuvant chemotherapy

3. What is tumour necrosis rate?

Answer 78

1. Chemotherapy
   Chemotherapy is the application of chemicals or drugs to kill cancer cells, and its effects are systemic.

i) Neoadjuvant Chemo
- provide rapid improvement in symptoms
- early treatment of micrometastatic disease
- facilitation of resection in responsive tumours
- allows time to manufacture customised endoprosthesis
- provides prognostic information about histological response- tumour necrosis %
Application 8-12 weeks pre surgery

ii) Adjuvant Chemo
- Treat micrometastases
- prolong disease free survival
Maintainence 6-12 months

Question 79

Radiotherapy

1. What is radiotherapy?
2. Usage of radiotherapy in sarcomas?
3. Name radiosensitve sarcomas.
4. Name radioresistant sarcomas.

Answer 79

1. Definition
   The use of high energy ionizing radiations (high energy photons-Xray or gamma ray) or charged particles (protons,electron, neutrons) to kill cancer cells and shrink tumours.

through
- indirect through production of free radicals- to cause DNA damage
- direct DNA damage

targets actively dividing cells

2. Usage
   a) For definitive control
   - Ewing sarcoma
   - Primary lymphoma of the bone
   - Hemangioendothelioma
   - solitary plasmacytoma of bone

b) Adjunct to surgical excision
- for soft tissue sarcoma
- given pre / post-operatively
- pre op > to shrink tumour
- post op > to prevent recurrence

c) palliative care
- reduce pain

d) and impending fracture fixation in metastatic bone disease
-needed after fixation of impending/pathologic fractures to reduce overall tumor burden.
- prostate tumors are very radiosensitive
- breast cancer is 70% sensitive, 30% resistant
** GI and renal tumors are not radiosensitive

3. Radiosensitive sarcomas
   Bone
   - Ewing sarcoma
   - Lymphoma of bone
   - Myeloma of bone

Soft tissue
- Rhabdomyosarcoma (emrbyonal)

4. Radioresistant
   Bone
   - Chondrosarcoma

Soft tissue
- Well-differentiated liposarcoma

Question 80

Radiotherapy

1. Difference between pre op and post op RT.
2. What are common complications of RT

Answer 80

1. pre op and post op RT

Pre op RT = neoadjuvant
- leads to more wound complications (40%)
- edema, fibrosis and joint stiffness is less (<15%)
-smaller radiation field
-allows formation of pseudocapsule to facilitate close margin resection.
-helps tumour shrink prior to surgery
-lower local recurrences rates

Post op RT = adjuvant
- less wound complications (<20%)
- More edema, fibrosis and joint stiffness is less (>15%)
- Larger radiation field
- no pseudocapsule advantages
- no shrinking of tumour
- higher local recurrence rates

2. Common complications of RT

a) Soft tissue complications
(early effects)
- edema
- delayed wound healing
- infection
- desquamation

(late effects)
- fibrosis joint
- stiffness
- secondary sarcoma
- fractures

b) Post-radiation sarcoma
- defined by the development of a sarcoma in a region previously radiated for malignancy
- incidence is ~13%
- more frequent in patients with prior chemotherapy

c) Post-radiation fractures
- approximately 25% incidence following soft tissue sarcoma resection and external beam irradiation
- risk factors
* radiation dose ≥ 59Gy
* weight bearing bones esp. femur
* female
* volume of bone receiving it
* anterior femoral compartment resection
* age
* periosteal stripping
* osteoporosis

Question 81

Principle of amputation in Oncological cases.

Answer 81

Amputation in oncology cases
Pre op assessment & preparation
1. Confirming diagnosis, local staging with MRI for evidence that limb is not salvageable
2. Determine level of amputation
3. Determine patient’s general medical condition – that fit to undergo surgery.
4. Optimise patient
5. Consent
6. Assess rehab potential
7. Psychological counselling for patient & relatives

Intra op principles of amputation
- Level of amputation: must be curative wide oncological margin
- Skin incision/muscle flap may need modification
- Frozen section may be required – to confirm specimen has clear margin of resection
- Avoid contamination of surgical field
- Bone, nerves, vessels handling are similar to other amputations.
- Meticulous hemostasis.
- Wound closure- avoid tension, pressure points
- Send specimen for repeat HPE eventhough have already done biopsy and results is known.
Post op management
- Good wound care
- Early adjuvant chemo/radiotherapy once wound has healed
- Adequate pain management
- Phantom limb pain/pain management
- Structured amputee rehabilitation
- Early definitive prosthesis
- Psychological care