Metastatic Cancer of Bone

Author: Patrick O'Donnell

Topic updated on 03/09/13 4:57pm

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 metastatic lesions include
    - axial skeleton (vertebral bodies, pelvis, ribs)
      - thoracic spine is most common site of bony metastasis
    - proximal limb girdle
      - proximal femur is most common site of fracture secondary to metastatic bone lesions
Pathophysiology
- mechanism of bone destruction (osteolysis)
  - osteolytic bone lesions are 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 are due to tumor-secreted endothelin 1
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
Associated conditions
- metastatic hypercalcemia
  - a medical emergency
  - symptoms include
    - confusion
    - muscle weakness
    - polyuria & polydipsia
    - nausea/vomiting
    - dehydration
  - treatment
    - treat with hydration and loop diuretics

Principles of metastasis

Mechanism of metastasis
- tumor cell intravasation
  - E cadherin cell adhesion molecule (on tumor cells) modulates release from primary tumor focus into bloodstream
- avoidance of immune surveillance
- target tissue localization
  - attaches to target organ endothelial layer via integrin cell adhesion molecule (expressed on tumor cells)
- extravasation into the target tissue
- 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 proximal limb girdles
- arterial tree metastasis
  - mechanism by which lung and renal cancer spread to the distal extremities

Symptoms

Presentation
- 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

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 survery
- 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
  - 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
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)

Treatment

Goals
- goal of treatment in metastatic disease is pain control and maintainence of patient independence
Nonoperative
- bisphosphonate therapy
  - indications
    - symtomatic care by preventing osteoclatic bone destruction
  - technique
    - IV pamidronate most commonly used
Operative
- stabilization of complete fracture, postoperative radiation
  - indications
    - most complete fractures are treated if operative stabilization leads to improved quality of life
  - 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
- neurologic decompression, spinal stabilization, and postoperative radiation
  - indications
    - metastatic lesions to the spine showing compression of neural elements and progressive neurologic deficits that are decreasing the quality of life
      - life expectancy of greater than six months
- preoperative embolization
  - indications
    - is indicated inpatients with renal cell carcinoma or thyroid carcinoma prior to operative intervention because these cancers are very vascular.

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

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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Qbank (25 Questions)

TAG

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

Review Topic

1. Enchondroma formation
2. Osteochondroma formation
3. RANK ligand induced tumor lysis
4. Osteoblastic bone metastases
5. Physeal bar formation

PREFERRED RESPONSE ▶

DISCUSSION: Endothelin 1 has been shown to be a crucial protein involved in the formation of osteoblastic bone metastases, like those caused by prostate cancer or certain types of breast cancer. Illustration A shows multiple osteoblastic type metastases in the spine of a patient with metastatic breast cancer. While the mechanistic explanation for this process isn't completely understood, it is known that tumor produced endothelin 1 is a necessary step in the development of osteoblastic metastasis.

Mohammad and Guise describe their cell-culture and mouse experiments which led to this discovery. Specifically, tumor produced cell media, containing tumor-produced factors like endothelin 1, had the ability to induce osteoblastic bone metastases in a mice treated with this culture media. In addition, this process was specifically inhibited by treatment with antagonists to endothelin 1, confirming the role of endothelin 1 in osteoblastic metastases.

Endothelin 1 has not been shown to play a role in enchondromas, osteochondromas, physeal bars, or RANK ligand induced tumor lysis.

Illustrations: A

REFERENCES:

1. Yuan J, Fuchs B, Scully S. Molecular basis of cancer. In: Einhorn TA, O'Keefe RJ, Buckwalter JA, eds. Orthopaedic Basic Science: Foundations of Clinical Practice. 3rd ed. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2007:379-393.

2. Mohammad KS, Guise TA. Mechanisms of osteoblastic metastases: role of endothelin-1. Clin Orthop Relat Res. 2003 Oct;(415 Suppl):S67-74. Review. PMID:14600594 (Link to Abstract)

Question Authors:

Patrick O'Donnell MD/PhD, Jan Szatkowski MD, Dave Marcu MD,

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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? Topic

Review Topic

FIGURES: A

1. Biopsy
2. Intramedullary stabilization
3. Intramedullary stabilization and send femoral reamings as biopsy
4. Palliative chemotherapy
5. Palliative radiotherapy

PREFERRED RESPONSE ▶

DISCUSSION: The radiographs show a cortically based lytic lesion in the mid diaphysis of the left femur, which is consistent with a metastatic lesion from a lung carcinoma, however without a history of biopsy proven bone metastasis, this lesion needs to be biopsied prior to definitive treatment. Sending femoral reamings is not an appropriate biopsy technique as significant contamination of the abductors, skin, and femoral canal occurs which compromises limb salvage if this lesion is in fact a sarcoma. The biopsy may be followed by intramedullary stabilization under the same anesthetic if the lesion can be confirmed as a carcinoma by the surgical pathologist. However if carcinoma cannot be confirmed, no further treatment is indicated until final pathology is available for review.

In both her JAAOS and ICL reviews, Weber et al discuss the evaluation, biopsy, and treatment of patients who present with destructive bone lesions, presumed to be related to metastatic disease. Her recommendations include biopsy of all destructive bone lesions without a history of known bone metastatic disease.

Rougraff reviews the workup of patients with carcinoma metastatic to bone. While making this diagnosis is a simple matter of obtaining tissue for the surgical pathologist, the correct diagnosis can be difficult, especially in GI lesions which may or may not appear on systemic staging studies. As such, systemic staging, bone scan, lab work, and physical examination become crucial to the diagnosis of metastatic carcinoma.

REFERENCES:

1. Weber KL. Evaluation of the adult patient (aged >40 years) with a destructive bone lesion. J Am Acad Orthop Surg. 2010 Mar;18(3):169-79. Review PMID:20190107 (Link to Abstract)

2. Weber KL, Lewis VO, Randall RL, Lee AK, Springfield D. An approach to the management of the patient with metastatic bone disease. Instr Course Lect. 2004;53:663-76. Review PMID:15116657 (Link to Abstract)

3. Rougraff BT. Evaluation of the patient with carcinoma of unknown origin metastatic to bone. Clin Orthop Relat Res. 2003 Oct;(415 Suppl):S105-9. Review. PMID:14600599 (Link to Abstract)

Question Authors:

Patrick O'Donnell MD/PhD, Jan Szatkowski MD, Ben Taylor MD,

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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? Topic

Review Topic

1. Increased apoptosis
2. Sustained angiogenesis
3. Tumor cell intravasation
4. Avoidance of immune surveillance
5. Genomic instability

PREFERRED RESPONSE ▶

DISCUSSION: All of the listed options are involved in the development of a malignant tumor with the ability to metastasize EXCEPT increased apoptosis. Apoptosis is programmed cell death, and tumor cells are known for their decreased rate of apoptosis. This allows for tumor cell sustained growth even after induction of cellular signals known to induce apoptosis in non-neoplastic cells.

Illustration A depicts the process of apoptosis.

Illustrations: A

REFERENCES:

1. Terek RM. Physiology of tumors. In: Menendez LR, ed. Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2002:3-9.

2. Zuscik MJ, Drissi MH, Chen D, Rosier RN. Molecular and cell biology in orthopaedics. In: Einhorn TA, O'Keefe RJ, Buckwalter JA, eds. Orthopaedic Basic Science: Foundations of Clinical Practice. 3rd ed. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2007:3-23.

Question Authors:

Patrick O'Donnell MD/PhD, John Badylak MD, Ben Taylor MD,

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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? Topic

Review Topic

FIGURES: A

1. Osteosarcoma
2. Chondrosarcoma
3. Primary lymphoma of bone
4. Metastatic carcinoma
5. Multiple myeloma

PREFERRED RESPONSE ▶

DISCUSSION: The clinical presentation, radiographs, and histology are most consistent with metastatic carcinoma. Metastatic carcinoma is the most common cause of a destructive bone lesion in older adults. Bone is the third most common site of metastasis, behind the lung and liver. Osteosarcoma occurs predominately in the metaphysis, and is often associated with periosteal reaction. Patients with multiple myeloma will usually show elevated serum protein electrophoresis levels. The pathology slide shows a mixture of glandular cells and bone, representing metastatic gastric cancer. Osteosarcoma, chondrosarcoma, and primary lymphoma of bone lack the presence of glandular cells on histology.

REFERENCES:

1. Damron TA. Orthopaedic Surgery Essentials, Oncology and Basic Science. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:229-243.

2. Mirra JM. Bone Tumors. Philadelphia, PA: Lea and Febiger; 1989:1120-1145.

Question Authors:

Joshua Blomberg MD, Patrick McCulloch MD,

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(OBQ09.51) A 59-year-old female with a history of biopsy proven metastatic renal cell carcinoma presents with a thoracic spine lesion consistent with renal cell carcinoma. She has lower extremity weakness and sustained clonus bilaterally. What is the most appropriate management prior to surgery? Topic

Review Topic

1. Blood cultures
2. High dose IV methylprednisone
3. Arterial embolization
4. CT guided cryotherapy
5. Radiation therapy

PREFERRED RESPONSE ▶

DISCUSSION: This patient has a history of renal cell carcinoma which is one of the most common tumors that metastasizes to bone. Renal cell tumors are highly vascular tumors (along with thyroid) and can bleed heavily during biopsy or excision. As such, careful evaluation and consideration for arterial embolization is necessary prior to surgery.

Prabhu et al reported on 51 preoperative spine embolizations and reported that 80% of these lesions could be embolized effectively. Even after embolization, average blood loss was 2.5L for these cases. In conclusion, they argue that preoperative embolization of the feeder vessels is safe and effective and is indicated to prevent excessive blood loss in patients undergoing surgery of the spine with metastatic renal cell carcinoma.

REFERENCES:

1. Prabhu VC, Bilsky MH, Jambhekar K, et al: Results of preoperative embolization for metastatic spinal neoplasms. J Neurosurg 2003;98:156-164 PMID:12650400 (Link to Abstract)

2. Heary RF, Bono CM. Metastatic spinal tumors. Neurosurg Focus. 2001 Dec15;11(6):e1. Review. PMID:16463992 (Link to Abstract)

Question Authors:

Patrick O'Donnell MD/PhD, Derek Moore, John Badylak MD,

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(OBQ09.83) You are caring for a 63-year-old female with metastatic breast cancer to the lumbar spine. Her neurological examination shows significant weakness in leg function and she is having difficulty ambulating. Imaging shows significant neural element compression by the tumor and complete erosion of the L1 vertebrae. She has no other sites of metastatic disease and is otherwise healthy. What treatment option do you recommend to best maintain her function? Topic

Review Topic

1. Palliative therapy
2. Complete neural element decompression
3. Complete neural element decompression with instrumentation to stabilize the spine
4. Complete neural element decompression, instrumentation, and postoperative chemotherapy
5. Complete neural element decompression, instrumentation, and postoperative radiotherapy

PREFERRED RESPONSE ▶

DISCUSSION: Declining neurological function in patients with metastatic disease requires treatment. In their landmark study, Patchell et al. evaluated the treatment of spinal cord compression from metastatic cancer via a randomized, multi-institutional trial that assigned 101 patients to surgery with postoperative radiotherapy vs. radiotherapy alone. The primary endpoint was the ability to walk after treatment. Secondary endpoints included urinary continence, muscle strength, functional status, need for corticosteroids and opioid analgesics, and overall survival time. They found that direct neural element decompression plus postoperative radiotherapy was superior to treatment with radiotherapy alone for patients with spinal cord compression caused by metastatic cancer. Schmidt et al. and Klimo et al. reviewed the literature regarding single and multimodal treatment options for metastatic disease to the spine with and without direct spinal cord compression.

REFERENCES:

1. Schmidt MH, Klimo P Jr, Vrionis FD. Metastatic spinal cord compression. J Natl ompr Canc Netw. 2005 Sep;3(5):711-9. Review. PMID:16194459 (Link to Abstract)

2. Klimo P Jr, Kestle JR, Schmidt MH. Treatment of metastatic spinal epidural disease: a review of the literature. Neurosurg Focus. 2003 Nov 15;15(5):E1. Review. PMID:15323458 (Link to Abstract)

3. Patchell RA, Tibbs PA, Regine WF, Payne R, Saris S, Kryscio RJ, Mohiuddin M, Young B. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet. 2005 Aug 20-26;366(9486):643-8. PMID:16112300 (Link to Abstract)

Question Authors:

Patrick O'Donnell MD/PhD,

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(OBQ08.66) A 47-year-old female, otherwise in good general condition, has intractable back pain from metastatic breast cancer isolated to her spine. She has failed progressive multi-agent chemotherapy and hormone therapy. Her exam is normal except for slight sensory dysesthesia, hyperreflexic patellar tendons, and mild gait instability which she reports has been worsening. Cervical, thoracic, and lumbar MRI show an isolated metastatic lesion involving the T9 vertebral body with moderate cord compression of the ventral spinal cord. At this stage what is the best treatment? Topic

Review Topic

1. Change chemotherapy protocol to Cyclophosphamide, Hydroxydanurubicin, Oncovin, Prednisone
2. Posterior spinal decompression after vertebral body kyphoplasty
3. Thoracic corpectomy, instrumented spinal fusion, and postoperative radiotherapy
4. Radiation therapy
5. Palliative care unit

PREFERRED RESPONSE ▶

DISCUSSION: While this patient does have metastatic breast cancer and will likely eventually succumb to her disease, she has a life-expectancy of greater than one year (see below), is in intractable pain, and has a progressing neurologic deficit. Therefore surgical treatment is indicated. Because her compression is anterior, a thoracic corpectomy, instrumented spinal fusion, and postoperative radiotherapy is indicated.

A scoring system by Tokuhashi et al has been shown to be a valuable method to predict life expectancy. In this revised system, scores are given according to the table shown in illustration A. Total scores of 0 to 8, 9 to 11, and 12 to 15 predict a life expectancy of less than 6 months, 6 months or more, and 1 year or more, respectively. This patient is in good general condition (2 points), has no extraspinal bone mets (2 points), has an isolated spinal lesion (2 points), has no mets to internal organs (2 points), has breast cancer (5 points), and has a mild incomplete palsy (1 point). Therefore using the system by Tokuhashi et al, her total score is 14 points, and she has a life expectancy greater than 1 year.

Klimo et al emphasize that decompressive laminectomy alone carries all the risks associated with an invasive procedure and offers the patient little benefit unless it is used to remove disease isolated to the posterior elements.

Patchell in a landmark randomized clinical trial showed that direct decompressive surgery plus postoperative radiotherapy is superior to treatment with radiotherapy alone for patients with spinal cord compression caused by metastatic cancer.

Schmidt et al review the epidemiology and treatment of metastatic cancer to the spine, and point out that spinal cord compression may develop in 5% to 10% of cancer patients.

Advanced chemotherapy likely will not help as she has already failed multiagent chemo. Because the lesion is primarily anterior, a posterior decompression is not adequate and would remove any remaining intrinsic stability in her spine. While radiation therapy would eliminate some of her pain, it would not address the spinal compression, and is inferior to surgery plus postoperative radiotherapy. Finally, palliative care is always a consideration, but should be reserved for patients who desire that treatment or have a life expectancy of less than six months.

Illustrations: A

REFERENCES:

1. Schmidt MH, Klimo P Jr, Vrionis FD. Metastatic spinal cord compression. J Natl Compr Canc Netw. 2005 Sep;3(5):711-9. Review. PMID:16194459 (Link to Abstract)

2. Klimo P Jr, Kestle JR, Schmidt MH. Clinical trials and evidence-based medicine for metastatic spine disease. Neurosurg Clin N Am. 2004 Oct;15(4):549-64. Review. PMID:15450889 (Link to Abstract)

4. Tokuhashi Y, Ajiro Y, Umezawa N. Outcome of treatment for spinal metastases using scoring system for preoperative evaluation of prognosis. Spine (Phila Pa 1976). 2009 Jan 1;34(1):69-73. PMID:19127163 (Link to Abstract)

Question Authors:

Patrick O'Donnell MD/PhD, John Badylak MD,

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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? Topic

Review Topic

1. Breast
2. Lung
3. Thyroid
4. Gastrointestinal
5. Prostate

PREFERRED RESPONSE ▶

DISCUSSION: Metastatic bony lesions that occur distal to the elbows or knees are most likely to occur from primary lung followed by breast and kidney tumors. The exact molecular mechanism for this metastatic pattern is not known. It is unknown if acral metastases in isolation confer a negative prognosis or if its merely a reflection of an aggressive tumor, however when encountered, long term survival is unlikely.

REFERENCES:

1. Scwartz HS (ed). Orthopaedic Knowledge Update: Musculoskeletal tumors 2. American Academy of Orthopaedic Surgeons. Rosemont, IL. 2007, pp 353-357

Question Authors:

Patrick O'Donnell MD/PhD,

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(OBQ08.204) A 67-year-old retired male custodian complains of progressively worsening low back pain over the past 6 months. He has not seen a doctor in the past 15 years. He admits to a 40 pack year smoking history, fatigue, and an unintentional 15 pound weight loss over the past year. A radiograph of the pelvis is provided in figure A. Which of the following would most likely confirm the diagnosis? Topic

Review Topic

FIGURES: A

1. Urine immunoelectrophoresis (UPEP)
2. Thyroid biopsy
3. CBC and blood smear
4. Prostate biopsy
5. Renal ultrasound

PREFERRED RESPONSE ▶

DISCUSSION: The radiograph demonstrates osteoblastic lesions throughout the pelvis and lumbar spine. Bony metastatic lesions may be osteoblastic, osteolytic, or mixed. Lung, breast, prostate, renal, and thyroid are the five most common sites of origin. Prostate metastasis is strongly associated with osteoblastic lesions. Renal, lung and thyroid metastases are osteolytic, and breast metastases are mixed. Multiple myeloma (diagnosed by UPEP) is a purely lytic lesion. Rougraff discusses a diagnostic algorithm to approach bony metastasis of unknown origin including history, focused physical exam, laboratory exam, imaging, and tissue biopsy. He also states that skeletal metastasis of unknown origin (including lytic, blastic, and mixed lesions) most frequently originate from the lung or kidney.

REFERENCES:

1. Rougraff BT. Evaluation of the patient with carcinoma of unknown origin metastatic to bone. Clin Orthop Relat Res. 2003 Oct;(415 Suppl):S105-9. PMID:14600599 (Link to Abstract)

2. Greenspan A, Jundt G, Remagen W: Differential Diagnosis in Orthopaedic Oncology. Lippincott Williams & Wilkins: 2006.

Question Authors:

John Badylak MD,

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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? Topic

Review Topic

FIGURES: A

1. Chondrosarcoma
2. Giant cell tumor
3. Multiple myeloma
4. Chordoma
5. Renal Cell Carcinoma

PREFERRED RESPONSE ▶

DISCUSSION: The history and imaging studies, specifically the high power histology slide, suggest a metastatic renal cell carcinoma. Specifically the histology slides show the characteristic clear cell change and the pseudoaveolar pattern of renal cell carcinoma. The histology is not characteristic of chondrosarcoma, giant cell tumor, or multiple myeloma. Chordoma, while similiar in histologic appearance, occurs from cellular remnants of the notochord, not in the proximal tibia.

REFERENCES:

1. Dorfman H, Czerniak B (EDS). Bone Tumors. St. Louis, Mosby Publishing. 1998. PP 1009-1029.

2. Marcove R, Arlen M. (EDS). Atlas of Bone Pathology, Philadelphia, PA: JB Lippincott; 1992. PP. 522-530

Question Authors:

Patrick O'Donnell MD/PhD,

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(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? Topic

Review Topic

FIGURES: A

1. CT-guided biopsy of spinal lesion
2. Percutaneous kyphoplasty
3. External beam radiation
4. Intravenous antibiotics
5. Arteriography and embolization of the spinal lesion

PREFERRED RESPONSE ▶

DISCUSSION: The CT of the abdomen shows a renal mass. Renal cell carcinoma is extremely hypervascular and has a propensity to bleed profusely. Thus, many authorities recommend arteriography and embolization of the lesion prior to performing any surgery on a suspected renal metastatic lesion. The goal is to reduce blood loss in patients undergoing surgery for these hypervascular tumors. There is no need for a CT guided biopsy for several reasons: 1) because our suspicion is high for metastatic renal disease 2) decompression is indicated and we can obtain a biopsy during decompression 3) biopsies of metastatic renal lesions can lead to excessive bleeding. Percutaneous kyphoplasty and radiation would not alleviate her radicular symptoms and are not indicated. Her clinical picture and MRI are not characteristic of infection, and therefore antibiotics would not be indicated.

Sundaresan et al performed a case-control study of patients with renal mets to the spine treated with radiation alone or surgery +/- radiation. The median survival of the surgically treated patients was 13 months, compared with 3 months for those treated by radiation alone. In addition, a greater proportion of the surgically treated patients were benefitted neurologically (70%) compared with those treated by radiation (45%).

REFERENCES:

1. Sundaresan N, Scher H, DiGiacinto GV, Yagoda A, Whitmore W, Choi IS. Surgical treatment of spinal cord compression in kidney cancer. J Clin Oncol. 1986 Dec;4(12):1851-6. PMID:2431111 (Link to Abstract)

Question Authors:

Doug Nowak MD, Derek Moore, Michael Hughes MD,

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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? Topic

Review Topic

FIGURES: A

1. Total hip arthroplasty
2. Hemiarthroplasty
3. Sliding hip screw
4. Dynamically locked cephalomedullary nail
5. Statically locked cephalomedullary nail

PREFERRED RESPONSE ▶

DISCUSSION: The best choice of the listed options for treatment of this fracture would be a statically locked cephalomedullary nail. Note however that either a statically locked cephalomedullary nail or a proximal femoral replacement (intentionally not a listed option) would be acceptable treatment for this lesion.

Based on the location of the lesion, neither a total hip arthroplasty nor a hemiarthroplasty would be appropriate - unless a cemented long stem which bypasses the defect is available as a treatment option. A sliding hip screw is not an appropriate treatment choice because of the subtrochanteric nature of the fracture and the fact that the sliding hip screw does not biomechanically address subtrochanteric fractures. As this patient has significant bone loss, a dynamically locked nail is at risk of shortening, and only the statically locked nail will provide resistance to the torsional stress and angular displacement.

Jacofsky and Haidukewych review the management of pathologic fractures of the proximal femur, "...the most commonly affected bone with metastatic disease in the appendicular skeleton." While the recommended treatment for this subtrochanteric pathologic fracture is arguable between proximal femoral replacement and statically locked cephalomedullary nail, the authors advocate for internal fixation rather than replacement.

REFERENCES:

1. Jacofsky DJ, Haidukewych GJ. Management of pathologic fractures of the proximal femur: state of the art. J Orthop Trauma. 2004 Aug;18(7):459-69. PMID:15289695 (Link to Abstract)

Question Authors:

Patrick O'Donnell MD/PhD, Ben Taylor MD, John Badylak MD,

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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? Topic

Review Topic

1. Intramedullary nail removal and radiotherapy to the limb
2. Systemic chemotherapy and keep nail in place to prevent fracture
3. Wide proximal femoral resection and hemiarthroplasty followed by radiotherapy
4. Wide resection including hip disarticulation
5. Palliative care

PREFERRED RESPONSE ▶

DISCUSSION: Bone lesions require biopsy prior to treatment as placement of an intramedullary nail through a tumor contaminates the entire bone. In the treatment of metastatic lesions with an intramedullary nail, adjuvant radiotherapy has to be dosed over the entire bone due to implant contamination of the bone. In the case of chondrosarcoma, which is chemotherapy and radiotherapy resistant, wide resection will require some type of resection of the entire bone, meaning either a hip disarticulation or a total femoral resection - removing all contaminated tissue.

REFERENCES:

1. Scwartz HS (ed). Orthopaedic Knowledge Update: Musculoskeletal tumors 2. American Academy of Orthopaedic Surgeons. Rosemont, IL. 2007, pp 353-357

Question Authors:

Patrick O'Donnell MD/PhD,

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

Review Topic

1. Intravasation
2. Avoidance of immune surveillance
3. Target tissue localization
4. Induction of angiogenesis
5. Direct stimulation of osteoclasts

PREFERRED RESPONSE ▶

DISCUSSION: Malignant cell metastasis requires at a minimum tumor cell intravasation (entry into blood vessels), avoidance of immune surveillance, target tissue localization, and induction of angiogenesis. While tumor cells may stimulate osteoclasts in the process of tumor cell osteolysis, this is not a necessary step for metastasis. In addition, tumor cells do not directly stimulate osteoclasts, they indirectly stimulate them through osteoblast/stromal cell production of cytokines like RANKL.

REFERENCES:

1. Buckwalter JA, Einhorn TA, Simon SR (EDS): Orthopaedic Basic Science. American Academy of Orthopaedic Surgery. Rosemont, IL. 2000

2. Menendez LR (ed): Orthopaedic Knowledge Update: Musculoskeletal Tumors. American Academy of Orthopaedic Surgery. Rosemont, IL. 2002 pp305-312

Question Authors:

Patrick O'Donnell MD/PhD,

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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? Topic

Review Topic

FIGURES: A

1. Biopsy of lesion
2. Total elbow arthroplasty
3. Currettage and bone grafting
4. Percutaneous cement injection
5. Radiofrequency ablation

PREFERRED RESPONSE ▶

DISCUSSION: The radiograph demonstrates a solitary lesion of the supracondylar lesion of the humerus in a patient with history of localized breast cancer. Work-up shows this to be an isolated lesion. Biopsy must be performed to rule out primary bone malignancy before definitive treatment is performed.

Rougraff discuss the indications for operative treatment in patients with metastatic carcinoma. They argue the decision whether to perform prophylactic surgery depends on: 1) the biologic activity of the bone lesion; 2) the responsiveness of the bone lesion to medical and radiation therapy; 3) the anatomic location of the bone metastasis; 4) patient factors, such as overall health status, expected length of survival, compliance, and patient expectations and needs. They explore these 4 issues in detail and recommend a clinical approach to patients with skeletal metastases.

REFERENCES:

1. Rougraff B: Indications for operative treatment. Orthop Clin North Am 2000; 31: 567-57 PMID:11043097 (Link to Abstract)

Question Authors:

Greg Galano MD, Michael Hughes MD, John Badylak MD,

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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? Topic

Review Topic

FIGURES: A

1. Revise the left hip total arthroplasty with a cemented stem
2. Open reduction and internal fixation of the acetabular fracture
3. Rest, IV bisphosphanates and follow-up in 6 weeks
4. Radiation therapy
5. Technetium Tc 99 and CT of the chest, abdomen and pelvis

PREFERRED RESPONSE ▶

DISCUSSION: This question has a lot of bells and whistle distraction. Fundamentally, it is a question about what you do when you see a lytic lesion in the pelvis of a person with a risk for tumor, in this case Paget's disease. The images show a skeletal tumor of unknown origin. Therefore, you can discount every “treatment” answer. First, you need to diagnose her.

Rougraff et al prospectively obtained medical history, physical examination, routine laboratory analysis, plain radiography of the involved bone and the chest, whole-body technetium-99m-phosphonate bone scintigraphy, and computed tomography of the chest, abdomen, and pelvis and found this diagnostic strategy discovered the primary site 85% of the time. In contrast, the biopsy alone (without the workup) discovered the primary tumor only 35% of the time.

REFERENCES:

1. Rougraff BT, Kneisl JS, Simon MA: Skeletal metastases of unknown orgin: A prospective study of a diagnostic strategy. J Bone Joint Surg Am 1993;75;1276-1281. PMID:8408149 (Link to Abstract)

2. Menedez LR (ed): Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 323-329.

Question Authors:

Patrick O'Donnell MD/PhD, John Badylak MD,

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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? Topic

Review Topic

1. multiple myeloma
2. post-radiation sarcoma
3. metastatic bone disease
4. Paget's sarcoma
5. lymphoma

PREFERRED RESPONSE ▶

DISCUSSION: The following malignant bone tumors occur most frequently in patients 40-80-years old (in order of decreasing frequency): metastatic bone disease, myeloma, lymphoma, Paget's sarcoma, and post-radiation sarcoma. The skeleton is a common site for metastasis from several visceral carcinomas. Think BLTPK for sources of metastasis: breast, lung, thyroid, prostate, and kidney. The cited article by Rougraff et al recommends a work-up that includes a history and physical examination, routine laboratory analysis, plain radiography of the involved bone and the chest, whole-body bone scan, and computed tomography of the chest, abdomen, and pelvis. These should all be performed prior to biopsy. Using this diagnostic strategy they were able to identify the primary site of cancer in 85% of patients in their study.

REFERENCES:

1. Rougraff BT, Kneisl JS, Simon MA: Skeletal metastases of unknown origin: A prospective study of a diagnostic strategy. J Bone Joint Surg Am 1993;75:1276-1281. PMID:8408149 (Link to Abstract)

2. Rougraff BT. Evaluation of the patient with carcinom. a of unknown origin metastatic to bone. Clin Orthop Relat Res. 2003 Oct;(415 Suppl):S105-9. PMID:14600599 (Link to Abstract)

Question Authors:

Greg Galano MD,

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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? Topic

Review Topic

FIGURES: A

1. Sliding hip screw
2. Cephalomedullary nail
3. Proximal femoral locking plate
4. Hemiarthroplasty
5. Proximal femoral replacement

PREFERRED RESPONSE ▶

DISCUSSION: The clinical presentation is consistent with metastatic bone disease to the femur with a high risk of pathologic fracture in a patient with a limited life expectancy. Prophylactic fixation with a modern cephallomedullary interlocking nail protects the entire bone and allows for immediate weight bearing.

Jacofsky et al discuss the evaluation and treatment of metastatic pathologic lesions and fractures of the proximal femur. They report 50% will be at the femoral neck, 30% at the IT region, and 20% at the subtrochanteric region. They recommend optimal treatment consists of a stable implant that protects the entire bone and will allow for immediate weight bearing (as up to 50% of pathologic fractures may not heal).

Figure A and B show a large lytic lesion in the subtrochanteric region of the proximal femur which occupies the majority of the metaphyseal diameter. Illustration A demonstrates a cephallomedullary nail spanning a lesion in the peritrochanteric region of the left femur (of note this is a long nail which extends to the supracondylar region of the femur).

Incorrect Answers:
Answer 1: A sliding hip screw will not protect the entire bone.
Answer 3: A proximal femoral locking plate will not protect the entire bone and would not allow for immediate weight bearing.
Answer 4: Hemiarthroplasty will not protect the entire bone and is not necessary given that the pathologic lesion is in the subtrochanteric region.
Answer 5: Proximal femoral replacement is not indicated as it is an aggressive treatment typically reserved for the curative treatment of primary bone tumors.

Illustrations: A

REFERENCES:

1. Jacofsky DJ, Haidukewych GJ. Management of pathologic fractures of the proximal femur: State of the art. J Orthop Trauma 2004; 18: 459-469. PMID:15289695 (Link to Abstract)

Question Authors:

Anay Patel MD, Michael Hughes MD, Jan Szatkowski MD,

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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? Topic

Review Topic

FIGURES: A

1. Local radiation therapy
2. Intramedullary nailing only
3. Intramedullary nailing and chemotherapy
4. Intramedullary nailing, radiation therapy to the tumor site, and chemotherapy
5. Intramedullary nailing, radiation therapy to the entire femur, and chemotherapy

PREFERRED RESPONSE ▶

DISCUSSION: This patient is presenting with biopsy proven metastatic breast cancer and a pathological fracture. The treatment in this situation is intramedullary nailing with postoperative radiation therapy to the entire femur and chemotherapy.

Due to the process of placing the intramedullary nail, the treating surgeon contaminates the ENTIRE femur with breast cancer. The surrounding area is already contaminated with tumor cells from the fracture, however. While the intramedullary nail will stabilize the pathological fracture, it does nothing to control the local progression of breast cancer in this patient's leg. Local radiotherapy will not only improve the local control of disease but it will palliate the patient's cancer related pain.

Weber et al review bone metastasis to the femur and propose valuable treatment pearls for clinical decision making and the biology which prevents cancer bearing bones to heal properly despite appropriate mechanical stabilization.

Swanson et al review the role of the orthopaedic surgeon in evaluating and treating metastatic bone disease, paying close attention to the necessity to obtain a tissue diagnosis in the event of presumed metastatic disease PRIOR to proceeding with any treatment plan.

REFERENCES:

1. Weber KL, Lewis VO, Randall RL, Lee AK, Springfield D. An approach to the management of the patient with metastatic bone disease. Instr Course Lect. 2004;53:663-76. PMID:15116657 (Link to Abstract)

2. Swanson KC, Pritchard DJ, Sim FH. Surgical treatment of metastatic disease of the femur. J Am Acad Orthop Surg. 2000 Jan-Feb;8(1):56-65. PMID:10666653 (Link to Abstract)

Question Authors:

Patrick O'Donnell MD/PhD, Ben Taylor MD,

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(OBQ05.207) A 59-year-old female presents with a metastatic spinal tumor and has a lytic lesion in the T12 vertebral body. The process of bone resorption in her lytic lesion is mediated by Topic

Review Topic

1. Direct resorption of bone by tumor cells
2. Neoangiogenesis of the vertebral body
3. Macrophage-mediated bony destruction
4. Tumor induced activation of osteoclasts
5. Necrosis of the vertebral body

PREFERRED RESPONSE ▶

DISCUSSION: Metastatic tumors are thought to induce osteolysis not by direct resorption of bone (remember only osteoclasts can destroy bone) but rather by releasing osteoclastogenic inflammatory cytokines.

Okeefe et al present a Level 5 review that states TNFa, RANKL, IL-1b, and IL-6 are osteoclastogenic inflammatory cytokins. Among these, RANKL is the most notable and important cytokine. It binds to RANK, a surface receptor, and initiates osteoclastogenesis.

Goltzman presents a Level 5 review of the skeletal manifestations of malignancy. They report that by binding and neutralizing RANKL, osteoprotegrin (OPG) can diminish the production of functioning osteoclasts, and this factor has been shown to block bone resorption that is associated with malignancy.

Illustration A is a schematic representation of tumor-cell induced osteolysis.

Illustrations: A

REFERENCES:

1. O’Keefe RJ, Molecular Mechanisms of bone metastasis and therapeutic implications. Clin Orthop 2003, 415, S100 PMID:14600598 (Link to Abstract)

2. Goltzman D, Osteolysis and Cancer. J Clinical Investigation. May 2001, Vol 107, 1219 PMID:11375409 (Link to Abstract)

Question Authors:

Sam Cho MD, Derek Moore, Michael Hughes MD,

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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? Topic

Review Topic

1. Antegrade femoral nailing with reamings sent to pathology for analysis
2. Antegrade femoral nailing with adjuvant radiotherapy to the lesion
3. Minimally invasive plating of the femur for stabilization and open cementation of the lesion
4. Referral to medical oncology for chemo-radiotherapy
5. Lesion biopsy with further treatment based on the results of the biopsy

PREFERRED RESPONSE ▶

DISCUSSION: New lesions which are not diagnosed by imaging and require surgical intervention need to have an appropriate biopsy with treatment dictated by the results of the biopsy. While this patient has a significant tobacco history, incorrect treatment of this lytic bone lesion could affect both her overall morbidity and mortality. As an example, a lytic high-grade chondrosarcoma may look exactly like a metastatic lesion but requires wide surgical excision, not just stabilization of an impending pathological fracture. Intramedullary nailing of a chondrosarcoma would spread the tumor the entire length of the bone and likely require a major amputation, not a limb salvage operation.

REFERENCES:

1. Simon MA, Finn HA. Diagnostic strategy for bone and soft-tissue tumors. Instr Course Lect. 1994;43:527-36. PMID:9097183 (Link to Abstract)

2. Menendez LR (Editor): Orthopaedic Knowledge Update. American Academy of Orthopaedic Surgeons. Rosemont IL. 2002. page 232 -239

Question Authors:

Patrick O'Donnell MD/PhD,

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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. What is the next most appropriate step in management of this patient? Topic

Review Topic

FIGURES: A

1. Intramedullary nailing of the tibia and send canal reamings to pathology
2. Radiotherapy for palliative pain control as the risk for pathological fracture is very small
3. Open incisional biopsy
4. Chemotherapy and surgical stabilization with intramedullary nailing of the tibia
5. Radiotherapy and surgical stabilization with intramedullary nailing of the tibia

PREFERRED RESPONSE ▶

DISCUSSION: Treatment for musculoskeletal oncology depends on a correct tissue diagnosis, which in this patient requires an open incisional biopsy. Despite the concern that this lesion may represent a metastases from lung carcinoma, without tissue diagnosis, treatment cannot ensue. Regarding concerns for pathologic fracture, this patient would be best managed with no weight bearing until a diagnosis can be determined. If this lesion is a sarcoma, then despite the patient's pain and risk of pathologic fracture, neo-adjuvant chemotherapy and wide surgical resection will be needed for the best chance at local control and patient survival. While intramedullary nailing of the tibia and sending canal reamings to pathology may either appear appropriate or be performed at some centers, this procedure may contaminate the entire bone with tumor and make limb salvage nearly impossible if this is a sarcoma. If the incisional biopsy shows carcinoma, then intramedullary nailing with adjuvant radiotherapy would be completely appropriate.

REFERENCES:

1. Simon MA, Springfield D (eds): Surgery for bone and soft-tissue tumors. Philadelphia, PA, Lippincott-Raven, 1998, p 621-624

Question Authors:

Patrick O'Donnell MD/PhD, Michael Hughes MD,

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(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? Topic

Review Topic

1. Prostate < breast < thyroid < renal < lung
2. Renal < prostate < breast < thyroid < lung
3. Lung < renal < thyroid < breast < prostate
4. Thyroid < renal < lung < breast < prostate
5. Lung < renal < breast < prostate < thyroid

PREFERRED RESPONSE ▶

DISCUSSION: The life expectancy of patients with metastatic skeletal lesions is an important concept to understand in order to correctly counsel patients regarding expectations. The life expectancy of patients with metastatic lung carcinoma is shorter than all the other cancers presented above, with less than 50% of patients surviving more than 6 months from diagnosis of skeletal metastasis. In general, patients with breast, thyroid, and prostate carcinoma live longer than patients with other metastatic lesions and patients with renal cell carcinoma have a variable life expectancy, depending on their medical condition at the time of diagnosis. The median survival in patients with various types of metastatic bone disease is: 1) lung: 6 months; 2) renal: variable depending on medical condition but may be as short as 6 months or as long as 4-5 years with isolated bone metastasis; 3) breast: 24 months; 4) prostate: 40 months; 5) thyroid: 48 months.

Coleman reviews the skeletal complications of malignant bone disease discussing pathogenesis, pain generators, and potential treatment regimes. Specifically, patients with bone metastases tend to outlive patients with visceral involvement. Management aimed at prevention of fracture or treatment of bone related cancer pain can significantly improve the cancer related morbidity associated with their diagnosis. Aggressive treatment with bisphosphonates has been shown to improve quality of life and decrease skeletally related events.

REFERENCES:

1. Koval KJ (ed): Orthopaedic Knowledge Update 7. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 141-154.

2. Coleman RE. Skeletal complications of malignancy. Cancer. 1997 Oct 15;80(8 Suppl):1588-94. Review. PMID:9362426 (Link to Abstract)

Question Authors:

Patrick O'Donnell MD/PhD, Michael Hughes MD,

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(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? Topic

Review Topic

1. Gastrointestinal
2. Lung
3. Kidney
4. Prostate
5. Breast

PREFERRED RESPONSE ▶

DISCUSSION: Occult lytic metastatic adenocarcinoma to bone without an identified primary source after bone scan and CT of the chest, abdomen, and pelvis is most commonly of lung origin. CT of the chest/abdomen/pelvis correctly identifies the primary tumor in greater than 90% of cases. Rougraff et al discuss the diagnostic dilemma of unknown metastatic lesions in 40 patients and the diagnostic steps used to identify the primary tumor source. Their recommendations include history, physical exam, routine laboratory analysis, plain radiographs of the entire bone, chest x-ray, whole-body technetium 99 scan, CT of chest/abdomen/pelvis, and finally biopsy. Their series indicates that occult metastatic lesions not identified on routine staging studies were most likely of lung origin. While each diagnostic strategy identified the primary source in some patients, the CT of the chest/abdomen/pelvis was the most valuable diagnostic tool. In their ICL, Frassica et al review current recommendations for evaluation, treatment, and outcomes of patients with metastatic bone tumors. Shih et al reviewed 177 patients with skeletal metastases and found that in 30% of the patients, the primary carcinoma could not be diagnosed. Post-mortem studies identified lung as the most common site of occult tumor.

REFERENCES:

1. Rougraff BT, Kneisl JS, Simon MA. Skeletal metastases of unknown origin. A prospective study of a diagnostic strategy. J Bone Joint Surg Am. 1993 Sep;75(9):1276-81. PMID:8408149 (Link to Abstract)

2. Frassica FJ, Frassica DA, McCarthy EF, Riley LH 3rd. Metastatic bone disease: evaluation, clinicopathologic features, biopsy, fracture risk, nonsurgical treatment, and supportive management. Instr Course Lect. 2000;49:453-9. PMID:10829198 (Link to Abstract)

3. Shih LY, Chen TH, Lo WH. Skeletal metastasis from occult carcinoma. J Surg Oncol. 1992 Oct;51(2):109-13. PMID:1405649 (Link to Abstract)

Question Authors:

Patrick O'Donnell MD/PhD,

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2.0

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Cases

	Secondary Hyperparathyroidism with Pathological Fracture Rt.Distal Femur with Brown Tumours (C1518) Pathology - Treatment Consult - Metastatic Cancer of Bone HPI - History of trivial trauma to right thigh leading to pain and inability to bear w... Further management of the Fracture Femur and Options for Prophylactic Fixat...	1 day ago 10 responses
	Metastatic Spine Disease (C1028) Spine - - Metastatic Cancer of Bone HPI - The patient is an 85-year-old female, very active, with no history of prior canc... The patient is an 85-year-old female who presents with severe neck pain and...	2/18/2011 3 responses
	Renal cell carcinoma metastasis (C1164) Pathology - - Metastatic Cancer of Bone HPI - 68-year-old woman presents with slowly increasing knee and leg pain. Past histo... What treatment do you propose for this distal femur and tibial diaphyseal r...	3/6/2012 38 responses
	A tumor destroyed the posterior column/posterior wall and dislocated the hip (C1165) Pathology - - Metastatic Cancer of Bone HPI - 62-year-old male presents with a 6 month history of increasing buttock pain with... What treatment would you propose?	3/6/2012 4 responses
$http://upload.orthobullets.com/cases/1296/pathological fracture.jpg$	Pathological hip fracture (C1296) Pathology - Treatment Consult - Metastatic Cancer of Bone HPI - Pathological hip fracture 12 weeks ago. The treatment was a Gamma Nail at the ti... What about re-administration of Zolendronic acid?	10/18/2012 28 responses
	radial neck fracture (C1338) Pathology - Treatment Consult - Metastatic Cancer of Bone HPI - falling from body-height. pain-deformity.inability to move her elbow. no other... what is your approach to this injury	11/28/2012 91 responses 5

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Posts

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Evidence & References Show References

Level of Evidence 1 (Randomized Control Trial)

Patchell RA, Tibbs PA, Regine WF, Payne R, Saris S, Kryscio RJ, Mohiuddin M, Young B. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet. 2005 Aug 20-26;366(9486):643-8. PMID:16112300 (Link to Abstract)

Level of Evidence 3 (Retrospective Cohort Study or Case-Control Study)

Sundaresan N, Scher H, DiGiacinto GV, Yagoda A, Whitmore W, Choi IS. Surgical treatment of spinal cord compression in kidney cancer. J Clin Oncol. 1986 Dec;4(12):1851-6. PMID:2431111 (Link to Abstract)

Level of Evidence 4 (Case Series)

Rougraff BT, Kneisl JS, Simon MA. Skeletal metastases of unknown origin. A prospective study of a diagnostic strategy. J Bone Joint Surg Am. 1993 Sep;75(9):1276-81. PMID:8408149 (Link to Abstract)
Shih LY, Chen TH, Lo WH. Skeletal metastasis from occult carcinoma. J Surg Oncol. 1992 Oct;51(2):109-13. PMID:1405649 (Link to Abstract)

Level of Evidence 5 and Other Journal Articles (includes Case Reports, Expert Opinions, Personal Observations, and Biomechanic Studies)

Mohammad KS, Guise TA. Mechanisms of osteoblastic metastases: role of endothelin-1. Clin Orthop Relat Res. 2003 Oct;(415 Suppl):S67-74. Review. PMID:14600594 (Link to Abstract)
Weber KL. Evaluation of the adult patient (aged >40 years) with a destructive bone lesion. J Am Acad Orthop Surg. 2010 Mar;18(3):169-79. Review PMID:20190107 (Link to Abstract)
Weber KL, Lewis VO, Randall RL, Lee AK, Springfield D. An approach to the management of the patient with metastatic bone disease. Instr Course Lect. 2004;53:663-76. Review PMID:15116657 (Link to Abstract)
Rougraff BT. Evaluation of the patient with carcinoma of unknown origin metastatic to bone. Clin Orthop Relat Res. 2003 Oct;(415 Suppl):S105-9. Review. PMID:14600599 (Link to Abstract)
Schmidt MH, Klimo P Jr, Vrionis FD. Metastatic spinal cord compression. J Natl ompr Canc Netw. 2005 Sep;3(5):711-9. Review. PMID:16194459 (Link to Abstract)
Klimo P Jr, Kestle JR, Schmidt MH. Treatment of metastatic spinal epidural disease: a review of the literature. Neurosurg Focus. 2003 Nov 15;15(5):E1. Review. PMID:15323458 (Link to Abstract)
Rougraff BT. Evaluation of the patient with carcinoma of unknown origin metastatic to bone. Clin Orthop Relat Res. 2003 Oct;(415 Suppl):S105-9. PMID:14600599 (Link to Abstract)
Jacofsky DJ, Haidukewych GJ. Management of pathologic fractures of the proximal femur: state of the art. J Orthop Trauma. 2004 Aug;18(7):459-69. PMID:15289695 (Link to Abstract)
Rougraff B: Indications for operative treatment. Orthop Clin North Am 2000; 31: 567-57 PMID:11043097 (Link to Abstract)
Jacofsky DJ, Haidukewych GJ. Management of pathologic fractures of the proximal femur: State of the art. J Orthop Trauma 2004; 18: 459-469. PMID:15289695 (Link to Abstract)
O’Keefe RJ, Molecular Mechanisms of bone metastasis and therapeutic implications. Clin Orthop 2003, 415, S100 PMID:14600598 (Link to Abstract)
Goltzman D, Osteolysis and Cancer. J Clinical Investigation. May 2001, Vol 107, 1219 PMID:11375409 (Link to Abstract)
Simon MA, Finn HA. Diagnostic strategy for bone and soft-tissue tumors. Instr Course Lect. 1994;43:527-36. PMID:9097183 (Link to Abstract)
Coleman RE. Skeletal complications of malignancy. Cancer. 1997 Oct 15;80(8 Suppl):1588-94. Review. PMID:9362426 (Link to Abstract)
Frassica FJ, Frassica DA, McCarthy EF, Riley LH 3rd. Metastatic bone disease: evaluation, clinicopathologic features, biopsy, fracture risk, nonsurgical treatment, and supportive management. Instr Course Lect. 2000;49:453-9. PMID:10829198 (Link to Abstract)

Textbooks

Review of Orthopaedics, 6th Edition, Mark D. Miller MD, Stephen R. Thompson MBBS MEd FRCSC, Jennifer Hart MPAS PA-C ATC, an imprint of Elsevier, Philadelphia, Copyright 2012
AAOS Comprehensive Orthopaedic Review, Jay R. Leiberman. Published by American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2009
Orthopaedic Knowledge Update 10, John M Flyn. Published by American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2011
Hoppenfeld SP. Surgical Exposures in Orthopaedics: The Anatomic Approach. Lipponcott, Williams, and Wilkins, Philadelphia, PA, Copyright 2009
Orthopaedic In-training Examination (OITE) Questions 2004-2012, American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2004-2012
Self-Assessment Examination (SAE) Questions 2004-2012, American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2004-2012
Yuan J, Fuchs B, Scully S. Molecular basis of cancer. In: Einhorn TA, O'Keefe RJ, Buckwalter JA, eds. Orthopaedic Basic Science: Foundations of Clinical Practice. 3rd ed. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2007:379-393.
Terek RM. Physiology of tumors. In: Menendez LR, ed. Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2002:3-9.
Zuscik MJ, Drissi MH, Chen D, Rosier RN. Molecular and cell biology in orthopaedics. In: Einhorn TA, O'Keefe RJ, Buckwalter JA, eds. Orthopaedic Basic Science: Foundations of Clinical Practice. 3rd ed. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2007:3-23.
Scwartz HS (ed). Orthopaedic Knowledge Update: Musculoskeletal tumors 2. American Academy of Orthopaedic Surgeons. Rosemont, IL. 2007, pp 353-357
Greenspan A, Jundt G, Remagen W: Differential Diagnosis in Orthopaedic Oncology. Lippincott Williams & Wilkins: 2006.
Scwartz HS (ed). Orthopaedic Knowledge Update: Musculoskeletal tumors 2. American Academy of Orthopaedic Surgeons. Rosemont, IL. 2007, pp 353-357
Buckwalter JA, Einhorn TA, Simon SR (EDS): Orthopaedic Basic Science. American Academy of Orthopaedic Surgery. Rosemont, IL. 2000
Menendez LR (ed): Orthopaedic Knowledge Update: Musculoskeletal Tumors. American Academy of Orthopaedic Surgery. Rosemont, IL. 2002 pp305-312
Simon MA, Springfield D (eds): Surgery for bone and soft-tissue tumors. Philadelphia, PA, Lippincott-Raven, 1998, p 621-624
Koval KJ (ed): Orthopaedic Knowledge Update 7. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 141-154.

Undefined

Mankin HJ, Mankin CJ, Simon MA. The hazards of the biopsy, revisited. Members of the Musculoskeletal Tumor Society. J Bone Joint Surg Am. 1996 May;78(5):656-63. PubMed PMID: 8642021. PMID:8642021 (Link to Abstract)
Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. 1980. Clin Orthop Relat Res. 2003 Oct;(415):4-18. PubMed PMID: 14612624. PMID:14612624 (Link to Abstract)
Damron TA. Orthopaedic Surgery Essentials, Oncology and Basic Science. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:229-243.
Mirra JM. Bone Tumors. Philadelphia, PA: Lea and Febiger; 1989:1120-1145.
Prabhu VC, Bilsky MH, Jambhekar K, et al: Results of preoperative embolization for metastatic spinal neoplasms. J Neurosurg 2003;98:156-164 PMID:12650400 (Link to Abstract)
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Metastatic Cancer of Bone

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