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Osteosarcoma
(OSA)
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Introduction
  • 85% of all bone tumors (50% of all bone tumors in small breeds).
  • 75% of all OSA affect the appendicular skeleton.
  • Most commonly affects distal radius; other common sites are distal femur, proximal tibia and proximal humerus.
  • Also affects axial skeleton and (rarely) soft tissues (extraskeletal OSA).
  • Appendicular OSA most common in large and giant breeds.
  • Signs : sudden onset lameness/metaphyseal swelling.
  • Treatment : surgery and chemotherapy.
  • Prognosis : poor long-term as metastatic spread common, if treated, good short-term prognosis.


Presenting signs
  • Acute onset lameness/metaphyseal swelling Osteosarcoma: distal radial swelling.
  • Pain on palpation.


Acute presentation
  • May (rarely) present with pathological fracture associated with minor trauma.


Age predisposition
  • Middle age to older (median 7 years).
  • Small peak in incidence at 18-24 months.


Sex predisposition
  • Males to females = 1.5:1.


Breed predisposition
  • Large and giant breeds:
    • Great Dane Great Dane.
    • Irish Wolfhound Irish Wolfhound.
    • Irish Setter Irish Setter.
    • Rottweiler Rottweiler.
    • Saint Bernard St Bernard.
    • Doberman Pinscher Dobermann.
    • German Shepherd dog German Shepherd Dog.
    • Golden Retriever Retriever: Golden.
Pathogenesis Top

Etiology
  • Unknown.


Predisposing factors
General
  • Size of animal: breeds weighing >35 kg are 60 times more at risk compared with breeds <10 kg.
  • Breeds 20-35 kg are 8 times more at risk compared with breeds <10 kg.


Pathophysiology
  • Affect metaphyseal areas of long bones. Most common site is distal radius (27%) followed by proximal humerus (27%), distal femur (14%), proximal (14%) or distal (7%) tibia. Thus the most common sites are 'away from the elbow, close to the stifle'.
  • Malignant tumor of bone cells.
  • Fast growing, rapidly metastasize to lungs Osteosarcoma: pulmonary metastases at post-mortem , spread to local lymph nodes is uncommon.
  • Radiographic evidence of metastasis to other bones in 6.4% of cases at time of diagnosis.
  • If treated with surgery and chemotherapy, 50% of cases develop bone metastases and 50%, pulmonary metastases Osteosarcoma: pulmonary metastases at post-mortem.


Timecourse (incubation, duration)
  • Untreated - most cases are euthanased withing weeks due to unremitting pain.

Diagnosis Top

Presenting problems
  • Lameness.


Client history
  • Acute onset lameness/swelling.
  • Fracture following minor trauma.


Clinical signs
  • Swelling at characteristic site.
  • Pain on palpation.


Diagnostic investigation

Radiography

  • Thoracic radiography Radiology: lungs  for evidence of pulmonary metastases Lung: cavitated mass (secondaries) - radiograph lateral.
    Tip Requires good radiographic technique. Anesthetize patient to allow manual inflation of lungs during radiographic exposure. Examine left and right lateral views carefully. Dorsoventral view may be useful if abnormalities detected on lateral projections.
  • <10% show radiographic evidence of pulmonary metastases at time of diagnosis, but >90% will have micrometastatic disease.
  • Limb radiography Bone: primary malignant tumor (distal radius) - radiograph - lesions may be primarily osteolytic or osteosclerotic or mixed (most common).
  • May have 'sunburst effect' and Codman's triangle (lifting of mineralized periosteum off the underlying cortex).
    No radiographic features are specific for osteosarcoma so a definitive diagnosis cannot be made on the basis of radiography alone.
  • OSA rarely crosses the joint.
  • Bone survey radiography (all long bones, spine and pelvis) has been shown to demonstrate evidence of bone metastases in 6.4% of all cases at the time of diagnosis.
  • Can present with pathological fracture Bone: pathological fracture (femur) - radiograph.
    No correlation between radiological appearance and prognosis.

Lymph node

  • Palpate local lymph node and take fine needle aspirates for cytology Cytology: fine needle aspirate or a biopsy for histopathology, if enlarged.

Histopathology

  • Bone biopsy - take multiple cores Bone biopsy 01  Bone biopsy 02  Bone biopsy 03  Bone biopsy 04  Bone biopsy 05  Osteosarcoma: bone biopsy 6 through central core and zone of transition for accurate diagnosis. If limb-sparing is likely, biopsy sites should be on craniolateral aspect of radius.
  • Use Jamshidi needle (8-11 gauge) Osteosarcoma: Jamshidi needle or a trephine through a key-hole incision. Jamshidi needle core biopsy has an accuracy rate of 92% for differention of neoplasia from other disorders and an accuracy rate of 82% for specific tumor type. Once core has been obtained it should be extracted from needle (using probe) in a retrograde manner to avoid crushing sample in tapered cutting end of needle.
    Trephine associated with an increased risk of fracture post-biopsy.
  • Active tumor is in center of lesion; periphery will be periosteal proliferation.
  • Needle cores can also be submitted for culture to rule out osteomyelitis Osteomyelitis.



Confirmation of diagnosis
Discriminatory diagnostic features
  • Radiography and signalment.

Definitive diagnostic features
  • Histopathology.


Gross autopsy findings
  • Swelling with bone proliferation/destruction in metaphyseal region.
  • Metastases in lungs, liver, kidney or bone.


Histopathology findings
  • Varying proportions of cartilage, osteoid and bone in spindle stroma.
    Tip Must see osteoid for the diagnosis Cytology: intracellular  osteoid - mandibular osteosarcoma.


Differential diagnosis

Acute lameness

  • Other primary bone tumors Bone: neoplasia.
  • Secondary bone tumors (metastatic lesions).
  • Osteomyelitis Osteomyelitis.
    • Fungal.
    • Bacterial.
  • Fractures.
  • Other injury/dislocation.

Treatment Top
Initial symptomatic treatment
  • Analgesia Analgesia: overview.
    Not very effective for bone pain.


Standard treatment
  • Excision of tumor (ie amputation) will remove source of pain. However, due to high incidence of micrometastatic disease at time of diagnosis, amputation alone is only a palliative procedure.
  • Survival times only increased if micrometastatic disease is controlled along with management of primary tumor. Most readily achieved by amputation with adjunctive chemotherapy. In select few cases, limb sparing surgery with adjunctive chemotherapy may be indicated and will provide survival rates comparable to amputation and chemotherapy.
  • Amputation should include the whole affected bone. Amputation at level of proximal humerus is advised for radial OSA and at level of proximal femur for tibial OSA. Humeral OSA requires forequarter amputation and distal femoral OSA requires amputation by coxofemoral disarticulation. Proximal femoral OSA will require amputation and hemipelvectomy to achieve clean margins of exision.
  • Limb amputation - most dogs cope very well (hindlimb amputation Amputation: hindlimb may pose fewer problems than forelimb Amputation: forelimb , but both are well tolerated).
    Must assess other orthopedic problems BEFORE amputation to ensure that dog will tolerate surgery.
  • Limb salvage by specialist surgeon: resection of affected bone and replacing with cortical allograft Osteosarcoma: limb salvage: intra-operative  Osteosarcoma: limb salvage: post-operative.
    Tip Only recommended for distal radial OSA.
  • Must be combined with chemotherapy Chemotherapy: general principles to justify procedure.
  • Chemotherapy with the platinum containing drugs (cisplatin Cisplatin or carboplatin Carboplatin ) can be started prior to, or soon after, definitive surgical treatment of primary lesion.
    Tip Implement standard safety precautions when handling any cytotoxic agent. Wear gloves, aprons and goggles and it is advisable to prepare the drugs over a plastic tray, with an absorbent liner, in a fume cupboard. NB These drugs, like most cytotoxic agents used in veterinary medicine, are not licensed for veterinary use.

Cisplatin Cisplatin :

  • Intravenous infusion of cisplatin 60-70 mg/m2 IV every 3 weeks for 4 doses (although ideal cumulative dose is not clear).
    Cisplatin has several potentially serious and life-threatening toxicities. Will cause renal failure if diuresis is not used. Renal function must be monitored with every treatment.
    Cisplatin causes intractable vomiting during administration. Must pretreat with butorphenol Butorphanol tartrate 0.4 mg/kg IM 30 min prior to treatment.
  • Agressive (18.3 ml/kg/h) saline diuresis needed 4 h pre-cisplatin and 2 h post. Cisplatin is administered slowly over 30 minutes and concurrently with the infusion.
    Pre-existing renal insufficiency is an absolute contraindication for cisplatin use.

Carboplatin Carboplatin :

    • 300 mg/m2 slow bolus IV over ten minutes every 3 weeks for 4 treatments.
    • Similar survival to cisplatin.
    • Renally excreted, so renal function must be normal prior to administration.
    • Diuresis not required, as carboplatin is not nephrotoxic.
  • Cisplatin and carboplatin are excreted through the kidneys.
    Advise owners to keep children away from pets' urine for at least 48 hours following cisplatin or carboplatin treatment.
    Additionally, dog should be encouraged to defecate and urinate away from areas frequented by
    children during this period and gloves should be worn to clean up accidental urine or fecal spillages in the home. Waste should be double-bagged prior to disposal.
  • Both cisplatin and carboplatin are myelosuppressive; carboplatin more so. Neutrophils and platelets are most commonly affected, with a nadir at 10-14 days following carboplatin treatment and a double nadir at 9 and 16 days following cisplatin treatment. Check neutrophil counts Hematology: neutrophil prior to each dose and delay treatment if neutropenia occurs. Treat clinically significant neutropenia aggressively with broad spectrum intravenous antibiotics Antimicrobial drug.
  • Palliative radiotherapy Radiotherapy shows an 80% response rate/improvement in limb function within 1-3 weeks. Median response duration,130 days. Pathologic fracture may occur (10-20% of dogs) with increased weightbearing.


Subsequent management

Sequelae Top
Prognosis
  • Very poor without treatment.
  • Pain of primary tumor will necessitate euthanasia within weeks of diagnosis.
  • Amputation alone will provide a median survival time of 18-25 weeks (50% survival at 6 months; 10% at 1 year).
  • Amputation + chemotherapy - best prognosis: 60% survival at 6 months; 33-55% at 1 year; 15-20% at 2 years. Median survival time, 9-11 months.
  • Serum alkaline phosphatase Blood biochemistry: alkaline phosphatase (ALP) above normal range at time of diagnosis is associated with a poorer prognosis and a median survival of 5-7 months.


Reasons for treatment failure
  • Chemotherapy not used.
  • Detectable metastatic spread at time of diagnosis. Chemotherapy not effective for gross (radiographically visible) metastatic disease.

Sources Top
Publications
Refereed papers
  • Recent references from PubMed.
  • Hillers K R, Dernell W S, Lafferty M H, Withrow S J & Lana S E (2005) Incidence and prognostic importance of lymph node metastases in dogs with appendicular osteosarcoma: 228 cases (1986-2003). JAVMA 226 (8), 1364-1367 PubMed.
  • Fuchs B & Pritchard D J (2002) Etiology of osteosarcoma. Clin Orth Rel Res 397, 40-52. PubMed
  • Dickerson M E, Page R L, LaDue T A et al (2001) Retrospective analysis of axial skeleton osteosarcoma in 22 large-breed dogs. JVIM 15, 120-124.PubMed
  • Langenbach A, McManus P M, Hendrick M J, Shofer F S & Sorenmo K U (2001) Sensitivity and specificity of methods of assessing the regional lymph nodes for evidence of metastasis in dogs and cats with solid tumours. JAVMA 218, 1424-1428.PubMed
  • Mehl M L, Withrow S J, Seguin B, Powers B E et al (2001) Spontaneous regression of osteosarcoma in four dogs. JAVMA 219, 614-617. PubMed
  • Blackwood L (1999) Bone tumours in small animals. JSAP 21, 31.
  • Ehrhart N et al (1998) Prognostic importance of alkaline phosphatase activity in serum from dogs with appendicular osteosarcoma - 75 cases (1990-1996). JAVMA 213, 1002-1006.PubMed
  • Bergman P J et al (1996) Amputation and carboplatin treatment of dogs with oesteosarcoma - 48 cases (1991 to 1993). J Vet Intern Med 10, 76-81.PubMed
  • McEntee M C et al (1993) Palliative radiotherapy for canine appendicular osteosarcoma. Vet Radiol 34, 367-370.
  • Ogilvie G K et al (1993) Evaluation of single-agent chemotherapy for treatment of clinically evident oesteosarcoma in dogs - 45 cases (1987-1991). JAVMA 202, 304-306.PubMed
  • Berg J et al (1992) Treatment of dogs with osteosarcoma by administration of cisplatin after amputation or limb-sparing surgery - 22 cases (1987-1990). JAVMA 200, 2005-2008.PubMed
  • Spodnick G J et al (1992) Prognosis for dogs with appendicular oesteosarcoma treated by amputation alone - 162 cases (1978-1988). JAVMA 200, 995-998.PubMed
  • Straw R C, Cook N L, LaRue S M, Withrow S J & Wrigley R H (1989) Radiographic bone surveys. JAVMA 195, 1458 (letter). PubMed
  • Powers B E, LaRue S M, Withrow S J, Straw R C & Richter S L (1988) Jamshidi needle biopsy for diagnosis of bone lesions in small animals. JAVMA 193, 205-210. PubMed
  • Carberry C A & Harvey H J (1987) Owner satisfaction with limb amputation in dogs and cats. JAAHA 23, 227-232.


Vetstream contributor(s)
  • Dr Laura Garrett DVM DipACVIM, School of Veterinary Medicine, Kansas State University, Manhattan, KS 66506-5606, USA.
  • Andy Moores BVSc CertSAS MRCVS, Department of Clinical Veterinary Science, University of Bristol, Langford House, Langford, Bristol BS40 5DU, UK.

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Amputation: forelimb
Amputation: hindlimb
Analgesia: overview
Antimicrobial drug
Blood biochemistry: alkaline phosphatase (ALP)
Bone: neoplasia
Butorphanol tartrate
Carboplatin
Cartilaginous exostosis
Chemotherapy: general principles
Chondrosarcoma
Cisplatin
Cyclophosphamide
Cytology: fine needle aspirate
Dobermann
Esophagus: neoplasia
Fibrosarcoma
Fracture: healing
Fracture: overview
German Shepherd Dog
Great Dane
Hematology: neutrophil
Hip: aseptic femoral headneck necrosis
Hip: infective arthritis
Hip: luxation
Irish Setter
Irish Wolfhound
Osteomyelitis
Osteosarcoma: axial skeleton
Osteosarcoma: bone biopsy 6
Radiology: lungs
Radiotherapy
Retriever: Golden
Rottweiler
St Bernard
Bone biopsy 01 Bone biopsy 02
Bone biopsy 03 Bone biopsy 04
Bone biopsy 05 Bone: pathological fracture (femur) - radiograph Link
Bone: primary malignant tumor (distal radius) - radiograph Link Carpus and paw: normal - radiograph DPa Link
Carpus and paw: normal - radiograph lateral Link Cytology: intracellular  osteoid - mandibular osteosarcoma Link
Lung: cavitated mass (secondaries) - radiograph lateral Link Osteosarcoma: distal radial swelling Link
Osteosarcoma: Jamshidi needle Link Osteosarcoma: limb salvage: post-operative Link
Osteosarcoma: limb salvage: post-operative Link Osteosarcoma: pulmonary metastases at post-mortem Link
Radius  ulna: bone tumor - pathology Link Radius: bone tumor - radiograph CrCd Link
Radius: bone tumor - radiograph lateral Link
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