Unknown origin tumours

Question 1

Describe metastatic cancer of bone?

Answer 1

• The commonest reason for a destructive bone lesion in adults
• cancers that spread to bone
  
  • breast
  • Lung
  • thyroid
  • renal
  • prostate
• ​Boneris 3rd commonest for metastatic disease ( after lung, liver)
• usually >40 yrs
• common sites
  
  • axial skeleton- thoracic spine most common site
  • proximal limb girdle
  • prox femur most common site of fx 2ary to met bone lesion

Question 2

What is the pathophysiology of bony mets?

Answer 2

• Mechanism of osteolysis
  
  • osteolytic bone lesions - caused by Tumour induced activation of osteoclasts
    
    • occurs thru RANK, RANKL, osteoprotegrin
  • Osteoblastic bone mets are due to tumour secreted endothelin 1

Question 3

What is the prognosis of pts with metastatic disease with thyroid, prostate, breast, kidney and lung?

Answer 3

• Thyroid 48 months
• Prostate 40 months
• Breast 24 months
• Kidney variable short as 6 months
• Lung : 6 months

Question 4

Name associated conditions of metastatic disease?

Answer 4

• Metastatic hypercalaemia
  
  • medical emergency
    
    • confusion
    • muscle weakness
    • polyuria/polydipsia
    • nausea/vomiting
    • dehydration
  • tx with hydration and loop diuretics

Question 5

describe the mechanism of metastasis?

Answer 5

• Tumour cell intravasation
  
  • E cadherin cell adhesion molecule on tumour cells modulates release from primary tumour focus into bloodstream
• Avoidance of immune surveillance
• target tissue localization
• induction of angiogenesis - via vascular endothelial growth factor (VEGF) expression
• genomic instability
• decreased apoptosis
• Vascular spread
  
  • Batson’s vertebral plexus
  • valveless venous plexus of the spine that provides a route of metastasis from organs to axial structure including vertebral bodies, pelvis, skull and prox limb girdles
  • Arterial tree metastasis
    
    • ​mechanism which lung/renal cancer spreads to distal extremities

Question 6

What are the symptoms of metastatic disease?

Answer 6

• Pain
  
  • mechanical due to bone destruction or tumorigenic pain at night
  • Pathological Fx 8-30%
  • metastatic hypercalcaemia
• ​O/E
  
  • Neurological deficit
    
    • compression of spinal cord with mets disease to spine

Question 7

Describe the workup for a pt with suspected metastatic diseasee?

Answer 7

• Plain radiographs
  
  • ​lung, thyroid & renal = lytic
  • 60% breast ca= blastic
  • 90% prostatic ca= blastic
  • lesions distal to elbow/knee often lung/renal primary- see pic
• CT chest /adbo/Pelvis
• Technetium bone scan- to detect extent of disease
  
  • myeloma & thyroid ca are cold
  • elevate with skeletal survey if cold
• Labs
  
  • U&E
  • ESR
  • LFT’s, CA, Phos, Alk Phosphatase
  • serum & urine immunoelectrophoresis
• Biopsy
  
  • shouldn’t tx bone lesion without tissue dx

Question 8

What is the goal of tx in metastatic disease?

Answer 8

• Control pain
• Maintainence of patient independence

Question 9

What is the tx of metastatic disease?

Answer 9

Non operative

• Bisphosphonates
  
  • symptomatic to prevent osteclastic bone destruction
  • iv pamidronate most commonly used

Operative

• Stabilisation of complete fx, postop radiation
  
  • most complete fx are treated if op stabilisatio leads to improved quality of life
  • post op radiation
    
    • all pts unless death immunent or area has had previous radiation
    • begin radiation after surgery
    • area of irradiation should include entire fixation device
• ​​Prophylatic stabilisation of impeding fx ( entire bone - ie nail) allow immediate WB, post op rdx
• preop embolization
  
  • ​renal cell carcinoma/thyroid as v vascular

Question 10

What is the tx for metastatic spinal lesion?

Answer 10

Non operative

• Palliative care
  
  • if life expectancy< 6months

Operative

• Neurological decompression, spinal stabilisation adn post op radiotherapy
  
  • for met lesions to spine with neurological deficits in pts with life expectancy > 6 months
  • preop embolisation included for renal ca to psine

Question 11

Are there any scoring systems to help decide prognosis of spinal mets and so tx?

Answer 11

• Tokuhashi et al Spine 2009. published a scoring system to help develop a treatment algorithm for patients with metastatic spinal lesions.
• They used a patient’s
  • general condition
  • number of extraspinal bone metastases
  • the number of metastases in the vertebral body,
  • the metastases to other major internal organs,
  • the primary site of the tumor,
  • degree of neurologic compromise to determine the life expectancy.
  • They recommended against surgical intervention for patients with less than six months to live.

Question 12

What is a Giant cell tumour?

Answer 12

• A Benign Agressive Tumour
• typically found in Epiphysis of long bones but may airse in apophysis ( like chondroblastomas)
• > females (cf most bone tumours)
• Age 30-50 yrs
• location
  
  • 50% around knee
  • **10% sacrum/vertebra body**
  • distal radius
  • phalanges also common
  • may a

Question 13

Describe the malignancy of gct?

Answer 13

• Primary malignant giant cell tumour
  
  • mets to lung in 2-5%
  • hand lesions have > chance of metastasis
• ​Secondary malignant giant cell tumour
  
  • ​occurs following radiation/multiple resections of GCT

Question 14

What are the symptoms of GCT?

Answer 14

• Pain refered to involved joint

O/E

• palpable mass
• decreased rom of joint

Question 15

What is seen on imaging a GCT?

Answer 15

Xrays

• An Eccentric Lytic Epiphyseal/Metaphsyeal lesion
• often extends into the distal epiphysis and borders subchondral bone

Bone scan

• Very hot

MRI

• Demarcation on T1 image between fatty marrow and tumour- see pic

Question 16

Describe the histology of GCT?

Answer 16

• Neoplastic cell is the mononuclear stromal cell- see pic
• Hallmark giant cells are numerous
• secondary aneurysmal bone cysts not unusual

Question 17

What is the tx of GCT?

Answer 17

Non operative

• Radiation alone
  
  • only inoperable/multiple lesions
  • 15%-> malignant transformation
• Medical Mx
  
  • Bisphosphonates
    
    • OC inhibitors- may decrease size of defect in GCT
  • Denosumab
    
    • Monoclonal antibody against RANKL
    • trails= decrease size of defect in GCT

Operative

• Extensive Currettage and Reconstruction ( w adj tx)
  
  • lesions amenable to currettage
  • hand lesions controversial
    
    • if no cortical defect- currettage + cement
    • if cortical defect- intercalary resection w fibular free graft vs amputation
    • need to preform extensive exterioration ( removal of large cortical window over lesion ) is required
  • Outcome 10-30% recurrence vs 3% w adjuvant tx ( phenol, hydrogen peroxide)

Question 18

What is Ewing’s sarcoma?

Answer 18

• A distinctive round cell bone sarcoma
• 5-25 yrs
• 2nd most common bone tumour in children
• Uncommon in african americans/chinese
• 50% Diaphysis of long bones
• locations
  
  • Pelvis, distal femur, proximal tibia, femoral diaphysis, proximal humerus
• Genetics
  
  • t( 11:22) translocation - in all cases
  • which leads to -> Fusion protein ESW-FLI1= identified w PCR

Question 19

What is the prognosis of Ewing’s sarcoma?

Answer 19

• 60-70% long term survival w isolated extremity disease
• 40% long term survival w pelvic lesions
• 15% long term survival if presents w mets

Poor prognostic factors

• Spine & pelvic tumours
• tumour >100cm3
• <90% necrosis w chemo
• elevated lactic dehydrogenase levels
• p53 mutation in addition to T(11:22) translocation

Question 20

What is the symptoms of Ewing’s sarcoma?

Answer 20

• Pain accompanied by fever
• often mimics infection

O/E

• Swelling and local tenderness

Question 21

What are the signs of Ewing’s sarcoma on imaging?

Answer 21

Xray

• Large destructive lesion in Diaphysis/metaphysis with a Moth eaten appearance- see pic
• Lesion maybe purely lytic or somereactive bone formation
• Periosteal reaction= onion skin/sunburst appearance

Bone Scan

• Hot lesion

MRI

• often shows large soft tissue component

CT chest

• Bony Mets

Question 22

What is seen on lab results with Ewing’s sarcoma?

Answer 22

• Elevated WCC
• Elevated ESR
• Anaemia Common
• Lactic Dehydrogenase
• Bone marrow biopsy- to rule out mets in marrow

Question 23

What is seen on histology with Ewing’s sarcoma?

Answer 23

• Gross- may have liquid consitency like pus
• sheets of monotomous small round blue cells- see pic
• prominent nuclei and minimal cytoplasm
• may have pseudo-rosettes ( circle cells w necrosis in centre)
• Immunostaining
  
  • CD99 reactivity

Question 24

Describe the tx for ewing’s sarcoma?

Answer 24

• Operative
  
  • Chemotherapy and Limb Salvage Resection
    
    • standard most pts
    • preop chemo 8-12 wks then surgery then chemo 6-12 mo post
    • Curent trend away radiotx
    • only with resectable tumours/mets

Question 25

What are the age differentials of small- round cell tumours?

Answer 25

* \<5 yrs= Neuroblastoma/ Leukaemia * 5-10 yrs= Esosinophilic Granuloma * 5-30 yrs= Ewing's sarcoma * \>30 yrs= lymphoma * \>50 yrs= myeloma

Question 26

What is an Adamantioma?

Answer 26

* A **rare low grade Malignant tumour of unknown aetiology that is almost always located in the mid-tibia** * \<300 cases documented * young adults 20-40 yrs

Question 27

Name associated conditions of adamantinoma?

Answer 27

* **Osteofibrous dysplasia** * _not a precusor_ of adamantinoma * a BENIGN, fibro-osseous lesion in the tibia cortex of young children * Tx by observation

Question 28

What is the prognosis of adamantinoma?

Answer 28

* May metastatize to lungs **25%** * so _longterm follow up is recommended_ * reocurrance is uncommon with negative margin excision

Question 29

What are the symptoms of adamantinoma?

Answer 29

* Pain of months- years duration O/E * **Bowing deformity** of tibia * **Palpable mass** of tibia

Question 30

What is seen on imaging of adamantinoma?

Answer 30

* xray * **Multiple sharply circumscribed lucent lesions "soapy bubbles" with interspersed sclerotic bone in mid tibia** * some lesions mat destroy cortex * may see bowing of tibia * radiographic evolution of lesion helpful as lesions may continue to grow and erode cortex * No periosteal reaction

Question 31

What is seen in histology of adamantiomas?

Answer 31

* Fibrous and epithelial tissue in gland like pattern * **nests of epithelial like cells** arranged in palisaing or **glandular pattern** * background of stroma

Question 32

What is the tx of adamatiomas?

Answer 32

* Operative * **Wide margin surgical resection** * most pts * often requires intercallary resection w allograft /megaprosthesis reconstruction * **Chemo and Radiotx typically not used**