Updated: 11/26/2020

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
https://upload.orthobullets.com/topic/8045/images/600px-hanleypathfx.jpg
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Introduction

  • Overview 
    • metastatic bone disease is a pathologic processes that is the most common cause of destructive bone lesions in adult patients   
    • treatment is aimed at controlling pain, maintaining patient independence, and preventing fractures.
  • Epidemiology  
    • incidence   
      • bone is the third most common site for metastatic disease (behind lung and liver) 
    • demographics 
      • Age >50-years-old 
    • location  
      • most common sites of bony metastatic lesions include spine > proximal femur > humerus 
        • pathologic fractures secondary to metastatic disease most commonly occur in the proximal femur, followed by the proximal humerus  
          • 65% nonunion rate
          • 50% in femoral neck, 20% pertrochanteric, 30% subtrochanteric
      • acral (distal extremities) lesions are rare, but when present are most commonly from lung carcinoma  
      • lung primary is the most common for occult metastatic disease 
    • risk factors  
      • carcinomas that commonly spread to bone include 
        • breast
        • lung
        • thyroid
        • renal
        • prostate 
          • mnemonic: BLT and a Kosher Pickle" 
  • Pathophysiology 
    • 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
    • lytic lesions  
      • osteolytic bone lesions "viscious circle"   
      • tumor cells secrete PTHrP which stimulates the release of RANKL from osteoblasts 
      • RANKL then binds to the RANK receptor on osteoclasts precursor cells
      • differentiation to active osteoclasts occurs, which causes bony destruction 
        • TGF-B, ILGF-1, and calcium are released from resorbed bone, which stimulates tumor cells to release more PTHrP 
    • osteoblastic lesions  
      • prostate and breast cancer mets 
      • due to tumor-secreted endothelin-1(ET-1) 
        • binds to endothelin A receptor (ETAR) on osteoblasts and stimulates osteoblasts
        • ET-1 decreases WNT suppressor DKK-1  
          • activates WNT pathway, increasing osteoblast activity
  • Associated conditions 
    • metastatic hypercalcemia
      • a medical emergency 
        • symptoms include 
          • confusion
          • muscle weakness
          • polyuria & polydipsia
          • nausea/vomiting
          • dehydration
        • 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: 6-7 months 

Anatomy 
  • 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 
Presentation
  • 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
      • 90% of pathologic fractures require surgery
        • rarely have potential to heal 
    • 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
Imaging
  • Radiographs        
    • recommended views 
      • plain radiographs in two planes of affected limb including the joint above and below the lesion 
    • findings 
      • destructive lesions may be lytic, mixed, or blastic (sclerotic) 
        • lung, thyroid, and renal are primarily lytic
        • 60% of breast CA are blastic
        • 90% of prostate CA are blastic
      • cortical metastasis are common in lung cancer  
      • lesions distal to elbow and knee are usually from lung or renal primary   
  • CT 
    • indications
      • CT of chest / abdomen / pelvis shold be obtained to evaluate for a primary lesion in all patients >50-years-old with a single bone lesion
      • CT of the lesion may also be obtained to evaluate containmnent within cortical boundaries 
  • Technetium bone scan 
    • indications
      • may be used to indentify other skeletal lesions 
    • findings 
      • myeloma and thyroid carcinoma are often cold on bone scan because it evaluates osteoblastic activity
        • evaluate with a skeletal survey

Studies 

  • Labs
    • CBC with differential
    • ESR
    • BMP
    • LFTs
    • PT, PTT
    • electrolyte panel
      • Ca, Phos, alkaline phosphatase
    • serum and urine immunoelectrophoresis (SPEP, UPEP)
      • multiple myelmoa 
    • PSA
      • prostate CA 
    • LDH
      • lymphoma 
    • Urinalysis 
      • renal CA 
  • Invasive studies 
    • 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
    • Histology 
      • characteristic findings 
        • epithelial cells in clumps or glands in a fibrous stroma   
      • immunostaining 
        • 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   
  • Nonoperative
    • bisphosphonate therapy 
      • indications
        • used in lytic, blastic and mixed lesions 
      • outcomes 
        • reduces rates of skeletally related events 
        • decreased lysis and associated hypercalcemia 
    • Denosumab 
      • indications
        • bone metastases from solid tumors and multiple myleoma 
      • outcomes 
        • superior to zoledronic acid in preventing skeletally related events 
    • radiation therapy 
      • indications
        • palliation of pain and local tumor control 
      • outcomes
        • renal cell carcinoma is not radio sensitive 
    • chemotherapy and hormone therapy
      • see table of treatment based on cancer type 
  • Operative
    • stabilization of complete fracture, postoperative radiation  
      • indications
        • operative stabilization would lead to improved quality of life
        • failure of nonsurgical treatment and pain 
      • 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 
        • more than 50% destruction of the diaphyseal cortices
        • permeative destruction of the subtrochanteric femoral region 
        • >50-75% destruction of the metaphysis 
        • persistent pain after irradiation therapy
        • functional pain 
    • preoperative embolization
      • indications
        • renal cell carcinoma or thyroid carcinoma prior to operative intervention because these cancers are very vascular    
Techniques 
  • Bisphosphonate therapy 
    • technique 
      • both oral (clodronate) and IV (pamidronate, zoledronic acid) formulas avaliable 
    • complications
      • osteonecrosis of the jaw 
  • Denosumab 
    • technique 
      • convenient subcutaneous dosing 
    • complications
      • osteonecrosis of the jaw 
  • Radiation therapy 
    • technique 
      • external-beam radiation therapy given as multiple fractions or as a single fraction in high dose 
      • dosage adn fraction are determined by location, symptoms, and tumor volume 
  • Chemotherapy and hormone therapy 
    • technique 
      • dependent on primary lesion and receptor positivity 
  • Stabilization of complete and/or impending fractures, postoperative radiation
    • technique 
      • dependent on location  
        • proximal humerus 
          • arthroplasty or open reduction internal fixation 
        • humeral diaphysis 
          • intramedullary nail 
        • femoral neck   
          • arthroplasty/endoprosthetic replacement  
          • total hip arthroplasty should be performed if there are acetabular lesions 
          • hemi-arthroplasty adequate if no acetabular involvement 
        • peritrochanteric 
          • cephalomedullary device with +/- cement    
        • femoral diaphysis 
          • statically locked cephalomedullary nail 
    • outcomes 
      • humerus 
        • length of resected segment related to functional outcome 
      • femur 
        • arthroplasty has significantly lower failure rates compared to IMN and ORIF
        • higher dislocation rate with THA compared to hemiarthroplasty 
        • higher rates of infection seen with arthropalsty compared to nails 
  • Embolization
    • technique 
      • preoperative emoblization perfomred for renal and thryoid cancers 
      • reduces intraoperative blood loss without adverse effects on healing 
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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Technique Guides (6)
Questions (56)
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(OBQ15.109) A 59-year-old women with known metastatic lung cancer presents with acute left hip pain with ambulation, as shown in Figure A. She previously underwent a right lung lobectomy 2 years ago, which has been complicated by chronic chest pain. Her oncologist predicts an estimated life expectancy of 12-18 months. She currently lives independently and walks for 2 hours per day. What would be the most appropriate treatment and rehabilitation plan? Tested Concept

QID: 5794
FIGURES:
1

Observation; restrict activities with cane assistance as needed

1%

(30/3189)

2

Radiation therapy; partial weight bearing with crutch assistance

1%

(30/3189)

3

Prophylactic intramedullary nailing; non-weight bearing with crutch assistance

1%

(44/3189)

4

Prophylactic intramedullary nailing; full weight bearing with cane assistance

95%

(3016/3189)

5

Long stemmed total hip arthroplasty; full weight bearing with walker assistance and hip precautions

2%

(52/3189)

L 1 A

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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? Tested Concept

QID: 4762
FIGURES:
1

Radiotherapy.

2%

(59/3885)

2

Curettage, cemented dynamic hip screw fixation and radiotherapy.

1%

(36/3885)

3

Curettage, cancellous bone grafting, cephalomedullary fixation and radiotherapy.

5%

(183/3885)

4

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

15%

(584/3885)

5

Cemented hemiarthroplasty and radiotherapy.

77%

(2997/3885)

L 2 A

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

QID: 3633
1

Increased apoptosis

87%

(2080/2397)

2

Sustained angiogenesis

1%

(26/2397)

3

Tumor cell intravasation

3%

(66/2397)

4

Avoidance of immune surveillance

3%

(63/2397)

5

Genomic instability

6%

(155/2397)

L 1 B

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(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? Tested Concept

QID: 3625
FIGURES:
1

Biopsy

83%

(2344/2829)

2

Intramedullary stabilization

2%

(53/2829)

3

Intramedullary stabilization and send femoral reamings as biopsy

14%

(392/2829)

4

Palliative chemotherapy

0%

(9/2829)

5

Palliative radiotherapy

0%

(10/2829)

L 1 A

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

QID: 3594
1

Enchondroma formation

10%

(318/3325)

2

Osteochondroma formation

5%

(176/3325)

3

RANK ligand induced tumor lysis

17%

(550/3325)

4

Osteoblastic bone metastases

64%

(2127/3325)

5

Physeal bar formation

4%

(132/3325)

L 3 C

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(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? Tested Concept

QID: 3214
FIGURES:
1

Osteosarcoma

4%

(115/3115)

2

Chondrosarcoma

4%

(130/3115)

3

Primary lymphoma of bone

11%

(334/3115)

4

Metastatic carcinoma

79%

(2455/3115)

5

Multiple myeloma

2%

(68/3115)

L 2 B

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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? Tested Concept

QID: 600
FIGURES:
1

Chondrosarcoma

25%

(804/3251)

2

Giant cell tumor

19%

(621/3251)

3

Multiple myeloma

3%

(87/3251)

4

Chordoma

4%

(136/3251)

5

Renal Cell Carcinoma

49%

(1584/3251)

L 4 B

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(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? Tested Concept

QID: 548
1

Breast

4%

(106/2687)

2

Lung

79%

(2111/2687)

3

Thyroid

10%

(279/2687)

4

Gastrointestinal

3%

(90/2687)

5

Prostate

3%

(89/2687)

L 1 C

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(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? Tested Concept

QID: 833
FIGURES:
1

Total hip arthroplasty

1%

(6/575)

2

Hemiarthroplasty

2%

(10/575)

3

Sliding hip screw

1%

(5/575)

4

Dynamically locked cephalomedullary nail

11%

(62/575)

5

Statically locked cephalomedullary nail

84%

(484/575)

L 1 B

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(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? Tested Concept

QID: 869
1

Intramedullary nail removal and radiotherapy to the limb

3%

(18/644)

2

Systemic chemotherapy and keep nail in place to prevent fracture

12%

(80/644)

3

Wide proximal femoral resection and hemiarthroplasty followed by radiotherapy

22%

(143/644)

4

Wide resection including hip disarticulation

61%

(393/644)

5

Palliative care

1%

(6/644)

L 2 A

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

QID: 271
1

Multiple myeloma

10%

(197/2029)

2

Post-radiation sarcoma

0%

(8/2029)

3

Metastatic bone disease

87%

(1775/2029)

4

Paget's sarcoma

1%

(12/2029)

5

Lymphoma

2%

(33/2029)

L 1 A

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

QID: 151
1

Intravasation

7%

(47/664)

2

Avoidance of immune surveillance

3%

(19/664)

3

Target tissue localization

7%

(45/664)

4

Induction of angiogenesis

3%

(19/664)

5

Direct stimulation of osteoclasts

79%

(527/664)

L 1 C

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(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? Tested Concept

QID: 195
FIGURES:
1

Biopsy of lesion

95%

(1657/1743)

2

Total elbow arthroplasty

1%

(10/1743)

3

Currettage and bone grafting

3%

(50/1743)

4

Percutaneous cement injection

0%

(5/1743)

5

Radiofrequency ablation

0%

(7/1743)

L 1 A

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(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? Tested Concept

QID: 295
FIGURES:
1

Revise the left hip total arthroplasty with a cemented stem

3%

(36/1255)

2

Open reduction and internal fixation of the acetabular fracture

5%

(62/1255)

3

Rest, IV bisphosphanates and follow-up in 6 weeks

9%

(117/1255)

4

Radiation therapy

5%

(61/1255)

5

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

77%

(970/1255)

L 1 B

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(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? Tested Concept

QID: 1072
FIGURES:
1

Local radiation therapy

0%

(7/1804)

2

Intramedullary nailing only

11%

(204/1804)

3

Intramedullary nailing and chemotherapy

11%

(195/1804)

4

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

26%

(472/1804)

5

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

51%

(915/1804)

L 4 C

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(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? Tested Concept

QID: 951
FIGURES:
1

Sliding hip screw

2%

(13/688)

2

Cephalomedullary nail

90%

(618/688)

3

Proximal femoral locking plate

2%

(11/688)

4

Hemiarthroplasty

4%

(25/688)

5

Proximal femoral replacement

2%

(12/688)

L 1 C

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(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? Tested Concept

QID: 1130
1

Antegrade femoral nailing with reamings sent to pathology for analysis

4%

(73/1835)

2

Antegrade femoral nailing with adjuvant radiotherapy to the lesion

1%

(26/1835)

3

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

0%

(8/1835)

4

Referral to medical oncology for chemo-radiotherapy

2%

(32/1835)

5

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

92%

(1682/1835)

L 1 A

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(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? Tested Concept

QID: 1255
FIGURES:
1

Intramedullary nailing of the tibia and send canal reamings to pathology

9%

(159/1855)

2

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

1%

(12/1855)

3

Open incisional biopsy

84%

(1562/1855)

4

Chemotherapy and surgical stabilization with intramedullary nailing of the tibia

3%

(47/1855)

5

Radiotherapy and surgical stabilization with intramedullary nailing of the tibia

4%

(65/1855)

L 1 A

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