O&T: A Young Lady With Bone Pain, An Old Lady With Bone Pain Flashcards
Approach to Knee swelling in a 4 month old
- Infections
- Fever
- Chills / Rigor (Bacteraemia) - Transient synovitis (Reactive arthritis)
- Body response to external insult
- cannot distinguish between foreign / self-antigens
- common in children with immature immune development
- not immunocompromised - Progression? Static in size?
- Haemangioma: on / off change in size - Pain intensity at rest
- Rest pain vs Mechanical pain
Bone tumour
- Low incidence
- 1% of all malignancies
Classification:
1. Biological behaviour: ***Enneking (Benign / Malignant)
- Benign: Latent / Active / Aggressive
- Malignant: Low grade / High grade
- Tumour origin classification (Primary / Secondary)
- ***Primary (Benign / Malignant) (usually young people)
—> Bone
—> Cartilage
—> Marrow
-
**Secondary (usually elderly)
—> **Solid organ: Prostate, Kidney, Breast, Thyroid, Lung (記: PKBTL)
—> ***Haematological: Lymphoma, Leukaemia, Myeloma
***1. Biological behaviour: Enneking (Benign / Malignant)
Benign Latent lesions:
- Grow slowly during normal growth —> stop —> heals spontaneously
- Exostosis (Osteoma), Non-ossifying fibroma
Benign Active lesions:
- Progressive growth
- **Lipoma, **Aneurysmal bone cyst
Benign Aggressive (Borderline malignant) lesions:
- Infiltrate normal tissues but do not metastasise
- **Giant cell tumour, **Chondroblastoma, Fibromatosis
Malignant Low-grade:
- Infiltrate normal tissues, low potential to metastasise, low recurrent risk
- ***Chondrosarcoma, Parosteal osteosarcoma
Malignant High-grade:
- Infiltrate normal tissues, metastasise early (distant), high recurrent risk
- **Osteosarcoma, **Ewing’s sarcoma
Sarcoma
Arise from:
1. Bone: Osteosarcoma
2. Cartilage: Chondrosarcoma
3. Muscles: Leiomyosarcoma, Rhabdomyosarcoma
4. Fat: Liposarcoma
5. Vessels: Angiosarcoma
Most common sarcoma: Soft tissues (Fat, Smooth muscles)
Soft tissue tumour
Primary (Benign / Malignant), arise from Connective tissue (Mesoderm)
- Adipose tissue
- Vessels
- Fibrous tissue etc.
Secondary:
- Possible but extremely uncommon e.g. Ca lung
Staging of Musculoskeletal malignancy
Enneking’s classification (X detail):
1: Low grade, No metastasis
2: High grade, No metastasis
3: With metastasis
a: Intra-compartmental
b: Extra-compartmental
- 1a: low grade, intra-compartmental, no metastasis
- 1b: low grade, extra-compartmental, no metastasis
- 2a: high grade, intra-compartmental, no metastasis
- 2b: high grade, extra-compartmental, no metastasis
- 3: with metastasis
—> NOT classified according to Size, LN (∵ not spread via LN, but spread to Lungs)
Compartment
Space bound by natural barrier to local invasion / infiltration by tumours
Examples:
- Periosteum
- Inter-osseous membrane
- Inter-muscular septums
- Deep fascia
Deep compartments
Arm:
- Humerus
- Flexor compartment
- Extensor compartment
- Skin
- SC tissue
Forearm:
- Ulna
- Radius
- Flexor compartment
- Extensor compartment
- Skin
- SC tissue
Thigh:
- Femur
- Flexor compartment
- Extensor compartment
(- Adductor compartment)
- Skin
- SC tissue
Leg:
- Tibia
- Fibula
- Anterior compartment
- Lateral compartment
- Posterior compartment
- Skin
- SC tissue
***History taking of Bone tumours
- Usual complaints
- Mass
- Pain
- ***Pathological fracture - Alerting features
- Rapid growth
- **Constant pain, esp. **Rest pain / Night pain +/- Mechanical pain
- **Unexplained fever
- **Constitutional symptoms - Family history
- Less significant
- e.g. Chondrosarcoma in hereditary multiple exostosis (worry about malignant transformation)
***P/E of Bone tumours
- Local examination
- ***Region LN
- think about leukaemia / lymphoma - ***Liver / Spleen
Alerting signs:
1. Large size (>5cm)
2. Deep location
3. **Hard constituency
4. **Fixed to normal tissue
5. Dilated superficial vessels
6. **Presence of regional LN
7. **Liver / Spleen enlargement
Clinical signs suggestive of malignant mass:
1. **Hard, fixed
2. **Overlying skin changes e.g. ulceration
3. ***Hypervascularity
4. LN examination
***Investigations of Bone tumours
Aim:
- Establish diagnosis
- Devise management plan
- Staging tumour (local extent + metastasis)
- Surgical decision + planning:
—> Local tumour extent
—> Skip lesions
—> Proximity to major neurovascular branches
—> Vascularity of tumour (Angiogram to visualise blood supply to tumour —> can do embolisation)
- Blood tests
- **CBP, ESR, CRP
- LRFT
- **Bone profiles: ALP, Ca, PO4
—> **Primary bone tumour: Normal Ca
—> **Bone metastasis: ↑ Ca
- ***Tumour markers: LDH, AFP, Beta-HCG, CEA, SEP, PSA - Local examination
- XR —> **Codman’s triangle, Soft tissue mass showing **Sunray’s pattern
- CT
- MRI —> local extent of extension (i.e. soft tissue involvement) - ***Metastatic search
- Bone scan —> for bone metastasis, bone formation, bone blastic activity
- CT thorax + abdomen —> lung metastasis
- PET —> for ↑ metabolic activity, better if bone lesion is lytic - Biopsy (for Diagnosis)
- FNA
- Core needle biopsy (Tru-cut)
- Open (Incisional / Excisional) - Surgical planning
- Angiogram
***Framework for describing X-ray
- Bone involved
- single / multiple - Part of bone involved
- epiphyseal / metaphyseal / diaphyseal - Site of bone involved
- intramedullary: central / eccentric (e.g. in Giant cell tumour)
- cortical
—> Intramedullary + Extraosseously —> Soft tissue extension —> ***aggressive until proven otherwise - What tumour has done to bone
- **sclerotic (osteoblastic) / **lytic (osteolytic) / mixed
- ***cortical erosions
- expansile cortex - Matrix of lesion
- Osteoid matrix —> Bone forming tumour
- Cartilage matrix —> Cartilage tumour
—> ring + arc calcification
—> **spicules of calcification
- Fibrous matrix —> Fibrosseous tumour
—> **Ground glass calcification
—> e.g. Fibrous dysplasia, Osteofibrous dysplasia - Border of lesion
- well-defined (narrow zone of transition)
- ***ill-defined (wide zone of transition): moth eaten, permeative - Bone response to lesion (i.e. any sclerotic rim)
-
**Periosteal reaction
- e.g. **Codman’s triangle (Periosteal new bone formation), **Sunray’s appearance (滴墨化開: Ossified soft tissue mass), **Onion skinning (一層層)
- smooth: benign process
- irregular: aggressive process - Soft tissue abnormality
Radiological features of Malignant vs Benign lesion (SpC Revision)
Malignant / Aggressive:
- Ill-defined border (Permeative)
- Periosteal reaction (Sunburst, Onion skinning)
- Cortical destruction
- Soft tissue mass
- Large / Rapidly growing
Benign / Slow growing:
- Well-defined / Sclerotic border (since tumour slow growing, bone has time to react to tumour to form sclerosis)
- Expansile (to encapsulate mass)
- Trabeculation present
Biopsy
Types:
1. FNAC
2. Core biopsy (Tru-cut)
3. Open: Incisional / Excisional (complete removal)
Aim:
- Confirm Histological diagnosis
- Immunological study + Genetic study
—> predict treatment response to hormonal / target agents + guide systemic treatment
FNAC vs Core biopsy:
- FNAC: only Cytologic examination
- Core biopsy: Histologic examination: Both Cells + Intercellular matrix
Biopsy tract considered contaminated with tumour cells
—> need to be excised together with tumour with a wide margin
—> careful planning of biopsy very important
—> poorly designed biopsy —> converts limb sparing resection to amputation
***Consult / Refer to tumour specialist for management if suspect malignancy
***Important Non-neoplastic DDx
- Infection
- ***Osteomyelitis
- esp. TB - Metabolic disorders
- **Gout
- Paget’s disease
- **Renal osteodystrophy - Endocrine disorders
- **Hyperparathyroidism
- **Cushing’s disease
(From SpC O/T:
4. Primary / Secondary bone tumour
5. ***Multiple myeloma)
General treatment principle of bone tumours
Multidisciplinary
Aim:
- Complete removal of tumour + Save life (i.e. Cure)
- Saving life > Saving limb —> Limb salvage should not jeopardise survival rate
Treatment modalities:
- **Local: Surgery, Radiotherapy
- **Systemic: Chemotherapy, Hormonal, Immunotherapy
—> Single / Combination
Neoadjuvant:
- HDMTX
- Adriamycin
- Cisplatin
- VP-16, Ifosfamide (2nd line, for poor responder to above)
***Surgical excision
4 types
1. ***Intra-lesional (Intra-capsular)
- curettage
- only for benign lesions
- ***Marginal
- en bloc removal of tumour + capsule -
**Wide
- en bloc removal of tumour + capsule + reactive zone + surrounding margin of normal bone
- **gold standard for Sarcoma treatment - ***Radical
- en bloc removal of entire bone
- if have skip lesions
Tumour zones:
1. Tumour itself
2. Capsule
3. Reactive zone (Satellite lesions + Inflammatory cells e.g. NK cells)
After excision:
- Allograft
- Prosthetic knee joint
***Bone metastasis features
- 3rd most frequent site after Liver + Lung
- Life expectancy improved ∵ advances in chemotherapy, hormonal treatment, radiotherapy, bisphosphonate
- Incidence ↑
- 1/4 of cancer patients will eventually develop bone metastasis
Osteolytic metastasis:
Neovascularisation of primary tumour
—> Blood vessel invasion
—> Embolism: Multicell aggregate (Tumour cells + Lymphocytes + Platelets)
—> Arrest in bone compartment
—> Tumour cell growth
—> ***Local production of tumour peptides, PTH-rP
—> PTH-rP production enhanced by TGF-β (produced in normal bone remodeling)
—> Osteoclast activation
—> Osteolytic lesions
Process can be interrupted by neutralisation of PTH-rP / rendering tumour cells unresponsive to TGF-β experimentally
Vicious cycle theory: Secondary tumour expressed factors
—> Osteoblasts increase expression of RANKL
—> Osteoclasts causing osteolytic, release tumour GF
—> Attract more Secondary tumour expressed factors
—> Repeated osteolytic activity by Osteoclast
**Features on XR
1. Multiple **osteolytic intramedullary lesions
2. ***Thinning of cortex
Osteoblastic metastasis
- New bone may be laid down directly
- Mechanism unclear
- Potential mediators: TGF-β, BMP, Fibroblast growth factors, Plasminogen activator sequence, PSA
Pathophysiology:
- Seed and Soil theory: Bone (rich in cytokines) provide a conducive area (soil) for secondary tumour (seed) to grow in
(Web:
1. Osteoblastic primarily
- Prostate
- Medullary thyroid carcinoma
- Osteolytic primarily
- Thyroid
- Kidney - Mixed
- Breast
- Lung
- CRC)
***Clinical problems of Bone metastasis
- Malignancy
- Reduction / Loss of mobility —> Impaired QOL
- Chronic pain
- Psychological stress (∵ chronic pain)
- Dependency on strong analgesics with significant SE
- ***Hypercalcaemia problems
- ***Marrow failure —> Pancytopenia
- ***Pathological fractures
***Approach to Bone metastasis
Aim:
- **Diagnosis
- **Stage tumour
- Define possible treatment options
- ***Prognosis
- History
- P/E
- ***Primary site of complaint
- Sites of common metastasis from primary MST: Lung, LN, Bone
- Sites of primary malignancies with high risk of bone metastasis:
—> Lung, Breast, Thyroid, Prostate, Kidney
—> Haemotological malignancies
(—> Liver, Testis)
***Investigation of Bone metastasis
- Blood tests
- **CBP, ESR, CRP: to rule out infection
- **Bone profiles: ALP, Ca, PO4
- ***Tumour markers:
—> LDH, CEA
—> SEP (multiple myeloma)
—> PSA (Ca prostate, in male >50)
—> AFP (HCC, in chronic liver disease)
—> Beta-HCG (germ cell tumour, in female <50) - Local imaging
- XR
- CT / MRI - Staging
- Bone scan
- CT thorax + abdomen
- PET-CT - Other investigations as directed from history, P/E, preliminary investigations e.g. Colonoscopy, Upper GI endoscopy
- Biopsy
- Histological diagnosis
***Management principles of Bone metastasis
Metastatic disease = Systemic disease involvement —> Likely other hidden metastasis undetected
Systemic therapy should be considered if appropriate, but:
- some cancers do not have effective systemic treatment e.g. Ca Lung, HCC
- patients usually elderly who cannot tolerate SE / toxicity of chemotherapy
Surgery / RT:
- Local treatment —> Limited role for curative treatment
Treatment aims:
1. ***Potential cure (↑ survival)
- Chemotherapy / RT: Multiple myeloma, Lymphoma
- Complete excision: Isolated bone metastasis of cancer with better prognosis: RCC
- Palliative care (↑ QOL / ambulation)
- **Bone pain
- **Pathological fracture
- ***Neurological deficit e.g. spinal cord compression
***Palliative treatment modalities
- Systemic
- Chemotherapy
- Hormonal therapy
- Targeted therapy
- Bisphosphonate - Local
- Surgery: Stabilisation, Fixation (using IM nail), Cord decompression, Debulking, Prosthetic replacement
- Cement augmentation
- Radiotherapy
- Radio-frequency ablation - Adequate pain control
Pending Pathological fractures
Scoring system (記: SPLS):
1. Site
- upper limb: 1
- lower limb: 2
- peritrochanter: 3
- Pain
- mild: 1
- moderate: 2
- weight bearing: 3 - Lesion
- blastic: 1
- mixed: 2
- lytic: 3 - Size related to bone diameter
- <1/3: 1
- 1/3 - 2/3: 2
- >2/3: 3
12 full marks
- >7: ↑ risk of fracture
- >8: probability of fracture: warrants prophylactic fixation
- <8: conservative
- 8: dilemma
- 9: diagnostic
