Updated: 6/24/2019

Metastatic Disease of Extremity

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https://upload.orthobullets.com/topic/8045/images/Case H- femur (lung) - xray - parsons_moved.png
https://upload.orthobullets.com/topic/8045/images/Histology A - parsons_moved.png
https://upload.orthobullets.com/topic/8045/images/Case A - prox femur - T1 - parsons_moved.gif
https://upload.orthobullets.com/topic/8045/images/Case D - hand (lung) - xray -  parsons_moved.png
Introduction
  • Metastatic cancer is the most common reason for a destructive bone lesion in adults   
    • carcinomas that commonly spread to bone include
      • breast
      • lung
      • thyroid
      • renal
      • prostate
  • Epidemiology
    • incidence
      • bone is the third most common site for metastatic disease (behind lung and liver)
    • demographics
      • metastatic bone lesions are usually found in older patients (> 40 yrs)
    • locations
      • common sites of bony metastatic lesions include spine > proximal femur > humerus
        • most common site of mets is thoracic spine 
        • 2nd most common site of mets is proximal femur
          • proximal femur is also the most common site of fracture secondary to metastatic bone lesions
            • 65% nonunion rate
            • 50% in femoral neck, 20% pertrochanteric, 30% subtrochanteric
  • Pathophysiology
    • mechanism of bone destruction
      • osteolytic bone lesions
        • caused by tumor induced activation of osteoclasts
        • occurs through the RANK, RANK ligand (RANKL), osteoprotegrin pathway
        • PTHrP positive breast cancer cells activate osteoblastic RANKL production
      • osteoblastic bone metastases
        • due to tumor-secreted endothelin 1 
  • Associated conditions
    • metastatic hypercalcemia
      • a medical emergency
        • symptoms include
          • see presentation below
        • treatment
          • hydration (volume expansion)
          • loop diuretics
          • bisphosphonates
  • Prognosis
    • median survival in patients with metastatic bone disease
      • thyroid: 48 months
      • prostate: 40 months
      • breast: 24 months
      • kidney: variable depending on medical condition but may be as short as 6 months
      • lung: 6 months 
Principles of Metastasis
  • Mechanism of metastasis  
    • tumor cell intravasation
      • E cadherin cell adhesion molecule (CAM) on tumor cells modulates release from primary tumor focus into bloodstream
      • PDGF promotes tumor migration
    • avoidance of immune surveillance
    • 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)
    • extravasation into the target tissue
      • uses matix metalloproteinases (MMPs) to invade basement membrane and ECM
    • induction of angiogenesis
      • via vascular endothelial growth factor (VEGF) expression
    • genomic instability
    • decreased apoptosis
      • thrombospondin inhibits tumor growth
  • Mechanism of 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 proximal limb girdles
    • arterial tree metastasis
      • mechanism by which lung and renal cancer spread to the distal extremities 
  • Mechanism of bone lysis  
    • oncogenic cell releases cytokines IL-6, IL-11, PTHrP, TGF-beta
    • PTHrP and TGF-beta activate osteoblasts
    • osteoblasts secrete RANKL, that binds to RANK on osteoclasts and activates osteoclasts
  • Mechanism of bone sclerosis (prostate and breast mets) 
    • prostate cancer cells secrete endothelin 1 (ET-1)
    • ET-1 binds to endothelin A receptor (ETAR) on osteoblasts and stimulates osteoblasts
    • ET-1 decreasesWNT suppressor DKK-1
      • activates WNT pathway, increasing osteoblast activity
Symptoms
  • Symptoms
    • pain
      • may be mechanical pain due to bone destruction or tumorigenic pain which often occurs at night
    • pathologic fracture
      • occurs at presentation in 8-30% of patients with metastatic disease
    • metastatic hypercalcemia
      • confusion
      • muscle weakness
      • polyuria & polydipsia
      • nausea/vomiting
      • dehydration
  • Physical exam
    • neurologic deficits
      • caused by compression of the spinal cord in metastatic disease to the spine
Evaluation
  • Workup for older patient with single bone lesion and unknown primary includes    
    • imaging
      • plain radiographs in two planes of affected limb
      • CT of chest / abdomen / pelvis
      • technetium bone scan to detect extent of disease
        • myeloma and thyroid carcinoma are often cold on bone scan - evaluate with a skeletal survey
    • labs
      • CBC with differential
      • ESR
      • basic metabolic panel
      • LFTs, Ca, Phos, alkaline phosphatase
      • serum and urine immunoelectrophoresis (SPEP, UPEP)
    • biopsy 
      • in patients where a primary carcinoma is not identified, obtaining a biopsy is necessary to rule out a primary bone lesion        
        • should not treat a bone lesion without tissue diagnosis of the lesion 
      • metastatic adenocarcinoma not identified by CT of the chest, abdomen, and pelvis is most likely from a small lung primary tumor
Imaging
  • Radiographic
    • recommended views
      • AP and lateral of involved area
    • findings
      • purely lytic or mixed lytic/blastic lesions 
        • lung, thyroid, and renal are primarily lytic
        • 60% of breast CA is blastic
        • 90% of prostate CA is blastic
      • cortical metastasis are common in lung cancer  
      • lesions distal to elbow and knee are usually from lung or renal primary  
  • CT scan
    • helpful to identify metastatic lesions to the spine
  • MRI
    • useful to show neurologic compromise of the spine
Studies
  • Histology
    • characteristic findings
      • epithelial cells in clumps or glands in a fibrous stroma   
    • immunohistochemical stains positive
      • Keratin
      • CK7 (breast and lung cancer)
      • TTF1 (lung cancer)
  • Receptor status
    • can provide therapeutic targets during concomitant medical management
    • estrogen, progesterone, and HER2/neu receptor status is essential for treating metastatic breast cancer 
Treatment - General
  • Nonoperative
    • bisphosphonate therapy 
      • indications
        • symptomatic care by preventing osteoclatic bone destruction
      • technique
        • IV pamidronate most commonly used
    • chemotherapy, radiotherapy, and hormone therapy
      • see table of treatment based on cancer type 
  • Operative
    • stabilization of complete fracture, postoperative radiation  
      • goals of surgical treatment
        • patient survives operation
        • immediate full weightbearing
        • implant survival > patient survival
      • indications
        • most complete fractures are treated if operative stabilization leads to improved quality of life
      • technique
        • fixation method depends on location
          • See table of fixation methods by location 
      • postoperative radiation
        • all patients require postop radiation unless death is imminent or area has previously been irradiated
        • begin radiation therapy after surgery
        • area of irradiation should include the entire fixation device (e.g. entire femur after intramedullary nailing of femoral lesion)
    • prophylactic stabilization of impending fracture, postoperative radiation      
      • indications
        • impending fx that meets criteria
          • criteria for impending fractures 
    • preoperative embolization
      • indications
        • is indicated inpatients with renal cell carcinoma or thyroid carcinoma prior to operative intervention because these cancers are very vascular.   
Treatment - Proximal Femur Fractures
  • Treatment
    • operative
      • cemented hemiarthroplasty
        • indications
          • intracapsular fracture
        • use long stem if distal lesion present
      • THA
        • indications
          • acetabular involvement
      • cephalomedullary nail + currettage + cement  
        • pertrochanteric / subtrochanteric fractures
  • Techniques
    • prophylactic IM nailing of proximal femur lesions
      • indications
        • impending and complete peritrochanteric fractures that do not involve the femoral head
      • technique
        • statically locked cephalomedullary IM nail for peritrochanteric fractures 
    • hemiarthroplasty vs. total hip arthroplasty 
      • indications
        • both impending and complete pathologic fractures of the femoral head and neck can be management with replacement arthroplasty 
  • Complications
    • dislocation of prosthesis
      • THA > hemiarthroplasty
    • infection
      • higher for THA and hemiarthroplasty than nails 
    • nonunion of fracture
      • for cephallomedullary nails
Treatment - Proximal Humerus Fractures
  • pending
Differentials & Groups
 
Malignant lesion in older patient(1)
 
Multiple lesion in older patient(1)
 
Epithelial glands on histology
 
Benefits from Bisphonate therapy
 
Treatment is wide resection and radiation(2)
Metastatic bone disease
 
 
 
 
Myeloma
 
     
   
Lymphoma
 
           
Chondrosarcoma
               
MFH / fibrosarcoma
               
Secondary sarcoma
               
Pagets disease    
     
 
 
Fibrous dysplasia            
 
 
Synovial sarcoma        
     
 
Hyperparathyroidism    
           
Gomus tumor        
       
Soft tissue sarcomas (3)                
ASSUMPTIONS: (1) Older patient is > 40 yrs; (2) assuming no impending fracture (3) High-grade soft tissue sarcomas includes angiosarcoma, synovial sarcoma, liposarcoma, desmoid tumor, MFH/fibrosarcoma: exception is rhabdomysarcoma which is treated with chemotherapy and wide resection
 
 
IBank
  Location
Xray
Xray
CT
B. Scan
MRI
MRI
Histo(1)
Case A prox femur
 
Case B pelvis
 
   
Case C hand (thyroid CA)
 
     
Case D hand (lung CA)
 
   
Case E femur (lung CA)
 
     
Case F pelvis
 
     
Case G renal CA (angio)
 
     
(1) - histology does not always correspond to clinical case 

 

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Questions (51)
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(OBQ08.214) You are seeing a 53-year-old female for 1 year of increasing knee pain. She is otherwise healthy. Based on the imaging studies below (Figures A-D), what is your diagnosis? Review Topic

QID: 600
FIGURES:
1

Chondrosarcoma

25%

(732/2893)

2

Giant cell tumor

18%

(534/2893)

3

Multiple myeloma

3%

(81/2893)

4

Chordoma

4%

(120/2893)

5

Renal Cell Carcinoma

49%

(1411/2893)

ML 4

Select Answer to see Preferred Response

PREFERRED RESPONSE 5
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(OBQ13.127) A 65-year-old community-ambulatory patient complains of constant left hip pain that affects her activities of daily living. Staging studies confirm multi-focal disease. Biopsy results are shown in Figure A. Recent radiographs are shown in Figures B and C. Life expectancy is estimated at 1 year. What is the most appropriate treatment option? Review Topic

QID: 4762
FIGURES:
1

Radiotherapy.

2%

(50/3286)

2

Curettage, cemented dynamic hip screw fixation and radiotherapy.

1%

(32/3286)

3

Curettage, cancellous bone grafting, cephalomedullary fixation and radiotherapy.

5%

(156/3286)

4

Proximal femoral resection, replacement with allo-prosthetic composite and radiotherapy.

14%

(467/3286)

5

Cemented hemiarthroplasty and radiotherapy.

78%

(2558/3286)

ML 2

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

(OBQ06.260) What is the most common cause for an aggressive lytic bone lesion in a patient above 40-years-old? Review Topic

QID: 271
1

Multiple myeloma

9%

(146/1603)

2

Post-radiation sarcoma

0%

(8/1603)

3

Metastatic bone disease

88%

(1410/1603)

4

Paget's sarcoma

1%

(9/1603)

5

Lymphoma

2%

(29/1603)

ML 1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(OBQ04.252) A 65-year-old patient without a history of cancer presents with thigh pain and a lytic lesion in the left femur. A CT scan of the chest, abdomen, and pelvis as well as a bone scan show this to be an isolated tumor. Biopsy confirms adenocarcinoma. What is the most likely primary source of this patient's tumor? Review Topic

QID: 1357
1

Gastrointestinal

13%

(62/464)

2

Lung

64%

(298/464)

3

Kidney

3%

(15/464)

4

Prostate

9%

(44/464)

5

Breast

9%

(43/464)

ML 3

Select Answer to see Preferred Response

PREFERRED RESPONSE 2

(OBQ05.186) A 51-year-old female with known metastatic breast cancer presents with acute right thigh pain and inability to bear weight. A radiograph is shown in Figure A. A biopsy is performed that confirms metastatic breast cancer. What is the next step in management? Review Topic

QID: 1072
FIGURES:
1

Local radiation therapy

0%

(6/1477)

2

Intramedullary nailing only

11%

(168/1477)

3

Intramedullary nailing and chemotherapy

10%

(150/1477)

4

Intramedullary nailing, radiation therapy to the tumor site, and chemotherapy

27%

(400/1477)

5

Intramedullary nailing, radiation therapy to the entire femur, and chemotherapy

50%

(745/1477)

ML 4

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

(OBQ04.219) Which of the following correctly lists the life expectancy from least life expectancy to greatest life expectancy when a patient presents with metastatic carcinoma to bone? Review Topic

QID: 1324
1

Prostate < breast < thyroid < renal < lung

3%

(19/640)

2

Renal < prostate < breast < thyroid < lung

2%

(10/640)

3

Lung < renal < thyroid < breast < prostate

39%

(249/640)

4

Thyroid < renal < lung < breast < prostate

4%

(25/640)

5

Lung < renal < breast < prostate < thyroid

52%

(331/640)

ML 4

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PREFERRED RESPONSE 5

(OBQ06.40) All of the following are necessary steps in bony metastasis of a malignant cell EXCEPT? Review Topic

QID: 151
1

Intravasation

7%

(30/445)

2

Avoidance of immune surveillance

2%

(11/445)

3

Target tissue localization

6%

(25/445)

4

Induction of angiogenesis

3%

(12/445)

5

Direct stimulation of osteoclasts

81%

(361/445)

ML 1

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

(OBQ08.162) Metastatic bony lesions that occur distal to the elbows or knees are most likely to originate from which one of the following primary organs? Review Topic

QID: 548
1

Breast

4%

(86/2404)

2

Lung

79%

(1903/2404)

3

Thyroid

10%

(239/2404)

4

Gastrointestinal

3%

(81/2404)

5

Prostate

3%

(83/2404)

ML 1

Select Answer to see Preferred Response

PREFERRED RESPONSE 2

(OBQ04.150) A 62-year-old male with a 50-pack-year history of tobacco use presents with complaints of productive cough and increasing leg pain for the past 6 months. Proximal tibial radiographs are shown in Figures A and B, and are concerning for an impending pathologic fracture. CT of the chest, abdomen, and pelvis, and staging blood work are negative. MRI of the tibia shows a multi-focal cortically based lesion without significant soft tissue mass and whole body technetium bone scan shows this to be an isolated lesion. What is the next most appropriate step in management of this patient? Review Topic

QID: 1255
FIGURES:
1

Intramedullary nailing of the tibia and send canal reamings to pathology

7%

(107/1453)

2

Radiotherapy for palliative pain control as the risk for pathological fracture is very small

1%

(10/1453)

3

Open incisional biopsy

86%

(1254/1453)

4

Chemotherapy and surgical stabilization with intramedullary nailing of the tibia

2%

(35/1453)

5

Radiotherapy and surgical stabilization with intramedullary nailing of the tibia

3%

(42/1453)

ML 1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(OBQ06.84) A 65-year-old woman presents with elbow pain. Her radiograph is shown in the Figure A. The patient had a history of non-metastatic breast cancer 10 years ago which was treated successfully. Repeat mammogram, bone scan and CT scan of the chest, abdomen and pelvis demonstrate this to be an isolated lesion. What is the next most appropriate action in treatment? Review Topic

QID: 195
FIGURES:
1

Biopsy of lesion

96%

(1371/1428)

2

Total elbow arthroplasty

0%

(3/1428)

3

Currettage and bone grafting

3%

(37/1428)

4

Percutaneous cement injection

0%

(5/1428)

5

Radiofrequency ablation

0%

(4/1428)

ML 1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

(OBQ05.65) A 70-year-old man with a history of esophageal cancer presents to the emergency department with pain in his right femur. His right hip xray is shown in Figure A and B. His medical oncologist has estimated he has a life expectancy of less than 6 months. His activities are limited to walking around his house. Which of the following management options is most appropriate? Review Topic

QID: 951
FIGURES:
1

Sliding hip screw

2%

(11/506)

2

Cephalomedullary nail

90%

(455/506)

3

Proximal femoral locking plate

2%

(10/506)

4

Hemiarthroplasty

4%

(18/506)

5

Proximal femoral replacement

1%

(5/506)

ML 1

Select Answer to see Preferred Response

PREFERRED RESPONSE 2

(OBQ07.111) A 70-year-old female has unrelenting lower back pain and severe left anterior thigh pain. She has hip flexion weakness on the left that is limiting her ambulation. A representative image from her abdominal CT is shown below as well as a sagittal MRI of her spine. Nonoperative management has failed. What is the next appropriate step before performing an anterior corpectomy and stabilization of the spine? Review Topic

QID: 772
FIGURES:
1

CT-guided biopsy of spinal lesion

24%

(204/847)

2

Percutaneous kyphoplasty

1%

(8/847)

3

External beam radiation

4%

(36/847)

4

Intravenous antibiotics

2%

(13/847)

5

Arteriography and embolization of the spinal lesion

69%

(586/847)

ML 2

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

(OBQ06.109) A 53-year-old woman with a history of Paget's disease and bilateral total hip arthroplasties presents with left hip pain and dysuria. An AP pelvic radiograph and CT scan are shown in Figure A and B. What is the next most appropriate step in management? Review Topic

QID: 295
FIGURES:
1

Revise the left hip total arthroplasty with a cemented stem

2%

(23/1055)

2

Open reduction and internal fixation of the acetabular fracture

5%

(54/1055)

3

Rest, IV bisphosphanates and follow-up in 6 weeks

8%

(82/1055)

4

Radiation therapy

5%

(51/1055)

5

Technetium Tc 99 and CT of the chest, abdomen and pelvis

79%

(838/1055)

ML 1

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

(OBQ11.210) All of the following are known steps in the development of a malignant tumor with the ability to metastasize EXCEPT? Review Topic

QID: 3633
1

Increased apoptosis

87%

(1797/2065)

2

Sustained angiogenesis

1%

(19/2065)

3

Tumor cell intravasation

3%

(58/2065)

4

Avoidance of immune surveillance

2%

(48/2065)

5

Genomic instability

7%

(137/2065)

ML 1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

(OBQ07.172) A 69-year-old man with known metastatic lung cancer presents with a pathological fracture after a fall from standing height (Figure A). Which of the following options is the best choice for treating this fracture? Review Topic

QID: 833
FIGURES:
1

Total hip arthroplasty

1%

(4/411)

2

Hemiarthroplasty

2%

(8/411)

3

Sliding hip screw

1%

(4/411)

4

Dynamically locked cephalomedullary nail

12%

(48/411)

5

Statically locked cephalomedullary nail

83%

(341/411)

ML 1

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

(OBQ11.202) A 65-year-old male is seen for increasing thigh pain and a new femoral lesion seen by his oncologist. A current radiograph is shown in Figure A. He has a known diagnosis of lung carcinoma but no history of metastatic disease. What is the next most appropriate step in management of this patient? Review Topic

QID: 3625
FIGURES:
1

Biopsy

84%

(2099/2492)

2

Intramedullary stabilization

2%

(40/2492)

3

Intramedullary stabilization and send femoral reamings as biopsy

13%

(321/2492)

4

Palliative chemotherapy

0%

(7/2492)

5

Palliative radiotherapy

0%

(9/2492)

ML 1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

(OBQ11.171) Endothelin 1 is known to be involved in which of the following disease processes? Review Topic

QID: 3594
1

Enchondroma formation

10%

(280/2876)

2

Osteochondroma formation

5%

(154/2876)

3

RANK ligand induced tumor lysis

16%

(470/2876)

4

Osteoblastic bone metastases

64%

(1839/2876)

5

Physeal bar formation

4%

(113/2876)

ML 3

Select Answer to see Preferred Response

PREFERRED RESPONSE 4

(OBQ05.244) What is the most appropriate treatment for a 65-year-old female with a 100-pack-year tobacco history who presents with a new painful lytic lesion in her femoral diaphysis? Review Topic

QID: 1130
1

Antegrade femoral nailing with reamings sent to pathology for analysis

4%

(55/1512)

2

Antegrade femoral nailing with adjuvant radiotherapy to the lesion

2%

(24/1512)

3

Minimally invasive plating of the femur for stabilization and open cementation of the lesion

1%

(8/1512)

4

Referral to medical oncology for chemo-radiotherapy

2%

(29/1512)

5

Lesion biopsy with further treatment based on the results of the biopsy

92%

(1385/1512)

ML 1

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

(OBQ07.208) A 56-year-old female is referred for a second opinion after placement of an intramedullary nail through a presumed metastatic lesion in her proximal femur. Final biopsy results from the lesion show a high-grade chondrosarcoma and staging studies show this to be an isolated site of disease. What treatment should be recommended? Review Topic

QID: 869
1

Intramedullary nail removal and radiotherapy to the limb

3%

(12/367)

2

Systemic chemotherapy and keep nail in place to prevent fracture

11%

(39/367)

3

Wide proximal femoral resection and hemiarthroplasty followed by radiotherapy

21%

(77/367)

4

Wide resection including hip disarticulation

64%

(235/367)

5

Palliative care

1%

(3/367)

ML 2

Select Answer to see Preferred Response

PREFERRED RESPONSE 4

(OBQ10.120) 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 the most likely diagnosis? Review Topic

QID: 3214
FIGURES:
1

Osteosarcoma

4%

(103/2787)

2

Chondrosarcoma

4%

(107/2787)

3

Primary lymphoma of bone

10%

(283/2787)

4

Metastatic carcinoma

80%

(2227/2787)

5

Multiple myeloma

2%

(56/2787)

ML 2

Select Answer to see Preferred Response

PREFERRED RESPONSE 4
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