Updated: 5/3/2021

Metastatic Cancer to Bone

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Introduction
  • Metastatic cancer is the most common reason for a destructive bone lesion in adults
    • bone is the third most common site for metastatic disease (behind lung and liver)
    • carcinomas that commonly spread to bone include
      • breast
      • lung
      • thyroid
      • renal
      • prostate
  • Age & location
    • metastatic bone lesions are usually found in older patients (> 40 yrs)
    • common sites of metastatic lesions include
      • axial skeleton (vertebral bodies, pelvis, ribs)
      • proximal limb girdle
        • proximal femur is most common site of fracture secondary to metastatic bone lesions
  • Mechanism 
    • mechanism of bone destruction (osteolysis)
      • metastatic bone destruction (causing osteolytic bone lesions) is caused by tumor induced activation of osteoclasts
        • occurs through the RANK, RANK ligand (RANKL), osteoprotegrin pathway 
    • mechanism of tumor metastasis
      • metastasis requires
        • tumor cell intravasation
        • avoidance of immune surveillance
        • target tissue localization
        • extravasation into the target tissue
        • induction of angiogenesis
        • genomic instability
        • decreased apoptosis
  • 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
  • Metastatic hypercalcemia
    • a medical emergency
    • treat with hydration and loop diuretics
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
    • malignant hypercalcemia
      • confusion
      • polyuria & polydipsia
      • nausea/vomiting
      • dehydration
  • Physical exam
    • metastatic hypercalcemia
      • muscle weakness
Evaluation
  • Workup for older patient with single bone lesion and unknown primary includes
    • imaging 
      • plain radiographs 
      • CT of chest / abdomen / pelvis
      • technetium bone scan
    • labs
      • CBC with differential
      • ESR
      • basic metabolic panel
      • LFTs, Ca, Phos, alkaline phosphataseserum 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
Imaging
  • Radiographic characteristics
    • purly lytic or mixed lytic/blastic lesions
      • 30% of lung CA is blastic
      • 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  
Histology
  • Characteristic findings of metastatic lesions
    • epithelial cells in clumps or glands in a fibrous stroma   
  • Immunohistochemical stains positive
    • Keratin
    • CK7 (breast and lung cancer)
    • TTF1 (lung cancer)
Treatment
  • Nonoperative
    • bisphosphonate therapy 
      • IV pamidronate prevents osteoclatic bone destruction
    • dexamethasone 
      • prevents progressive neurologic injury with spinal cord compression
    • radiation alone 
      • indications
        • indicated in radiosenstive tumors such as breast cancer, prostate cancer, multiple myeloma and lymphoma
        • indicated to shrink mets that are causing spinal cord compression 
  • Operative
    • prophylactic IM nailing or arthroplasty with adjuvent radiation
      • indications
        • impending fx that meets criteria
    • spinal neurologic decompression, stabilization, with postoperative radiation therapy   
      • indications
        • metastatic lesions to the spine showing compression of neural elements and progressive neurologic deficits that are decreasing the quality of life in patient with life expectancy of greater than six months
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 (3)

(M2.ON.15.4676) A 67-year-old woman presents to the emergency department for lower back pain and bilateral lower extremity weakness. Her symptoms began one day prior to presentation and are associated with decreased sensation in both of her legs and urinary incontinence. She was recently diagnosed with metastatic breast cancer. Her temperature is 99.0°F (37.2°C), blood pressure is 133/81 mmHg, pulse is 82/min, respirations are 15/min, and oxygen saturation is 98% on room air. Physical examination is notable for saddle anesthesia and 2/5 strength in the bilateral lower extremities. An MRI of the spine is shown in Figure A. Which of the following is the most appropriate next step in management?

QID: 107229
FIGURES:
1

Chemotherapy

0%

(0/4)

2

Dexamethasone

0%

(0/4)

3

Palliative pain management

25%

(1/4)

4

Radiation therapy

25%

(1/4)

5

Surgical decompression

50%

(2/4)

M 7 E

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(M2.ON.14.62) An 80-year-old male with known metastatic prostate cancer presents to your office with vague complaints of "achy bones." Strangely, he refers to you using the name of another physician. On physical exam, he is afebrile, but mildly tachycardic at 100 beats/min. Mucous membranes are dry. Cardiac exam shows regular rhythm and no murmurs. The patient has diffuse, nonfocal abdominal pain. He cannot articulate the correct date. You check the patient's serum calcium level, which is found to be 15.3 mg/dL. What is the best next step in management?

QID: 106435
1

Pamidronate

17%

(4/23)

2

Intravenous normal saline

61%

(14/23)

3

Calcitonin

4%

(1/23)

4

Furosemide

4%

(1/23)

5

Hemodialysis

9%

(2/23)

M 7 C

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