Osteogenic Sarcoma (Bone tumor)

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4/23/12

Osteogenic Sarcom(Osteosarcoma)

byMej Amm M. BatoonMedical Intern/Clerk



4/23/12

Osteosarcoma is the most commonmalignant bone tumor (accountsfor approximately 20% of primary

bone cancers), followed bychondrosarcoma and Ewingsarcoma. This disease is thought to

arise from primitive mesenchymalbone-forming cells, and its histologichallmark is the production of malignant osteoid.



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• Osteosarcoma is a deadly form of musculoskeletal cancer that mostcommonly causes patients to die

from pulmonary metastaticdisease.

• Most osteosarcomas arise as solitary

lesions within the fastest growingareas of the long bones of children.

• However, multiple sites may become

apparent within a period of about 6



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Most common primary bonemalignancy.

Accounts for almost 45% of all bonesarcomas

60-75% occur in children and

adolescentsVery rare in young children aged <5yo

Incidence increases steadily with age

Increases dramatically in adolescents

Osteosarcoma:

Epidemiology

O S

T E O G E N I C

S A

R C O M A



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• Has a bimodal age distribution:

– first peak during adolescence (10-14-year-old age group, coinciding with the

pubertal growth spurt)

– second peak in older adulthood (adultsolder than 65 years of age; it is more

likely to represent a second malignancy,frequently related to Paget's disease,bone infarcts and prior irradiation)

Osteosarcoma:

Epidemiology



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• Slightly higher in males than infemales (1.5-2 times in males than infemales)

• incidence is slightly higher in blacksthan in whites

Osteosarcoma:

Epidemiology



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• Commonly occurs inlong bones of extremities near

metaphyseal growthplates

• Most common sites:

– Femur (42%,with 75%in the distal femur)

– Tibia (19%, with 80% in

the proximal tibia)

Osteosarcoma:

Pathophysiology



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• Exact cause is unknown

• Usually associated with:

–

Rapid bone growth – Radiation exposure

– Genetic predisposition:

• Retinoblastoma – germ-line mutations in theRB gene (up to 1000x risk)

• Li-Fraumeni syndrome – germ-line p53mutation

• Pa et disease and other bone dysplasias

Osteosarcoma:

Etiology



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• Classic category (75%)

– Osteoblastic

–

Chondoblastic – Fibroblastic

Osteosarcoma:

Classification



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• Remaining 25% variants:

– Clinical characteristics

•

Osteosarcoma of the jaw• Postradiation osteosarcoma

• Paget’s Osteosarcoma

–

Morphologic characteristics• Telangiectatic osteosarcoma

• Small cell osteosarcoma

•

Epithelioid osteosarcoma

Osteosarcoma:

Classification



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• Most common presentingsymptom is pain andswelling of the affected

site• Pathologic fractures

common in

telangiectactic type of osteosarcoma

• Usually metastasize to

lungs, which rarely

Osteosarcoma:

Presentation



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• Mass: may be present or absent

• Decreased range of motion of

affected site• Lymphadenopathy: involvement of

local or regional lymph nodes is

unusual• Respiratory findings: auscultation is

usually uninformative unless thedisease is extensive

Osteosarcoma:Presentation on

Physical exam



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Imaging

Studies



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Plain Films

• Primary lesion

• Chest

–

posteroanterior (PA) – lateral chest views

• Osteosarcoma lesions can be purely

osteolytic (approximately 30% of cases), purely osteoblastic(approximately 45% of cases), or a

mixture of both.



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• Codmandescribed thisentity in 1909,

stating, "Inmany casesnear the

junction of thehealthy bonewith thetumor, there isa reactive new



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• Osteogenicsarcoma fibula.Destruction of

bone withsunburstappearance



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CT Scan

• CT scanning of the primary lesion

– To delineate the location and extent of the tumor

– Critical for surgical planning.

• CT scanning of the chest

–

More sensitive than plain filmradiography for assessing pulmonarymetastases

– Ideally done before performing a biopsyto avoid ambiguity that can arise from



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MRI

• MRI of the primary lesion

– Best method to assess the extent of intramedullary disease as well as

associated soft-tissue masses and skiplesions

• single most important study for

accurate surgical staging of thelesion with use of the Ennekingstaging system



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Bone Scan

• Radionuclide bone scanning withtechnetium-99 (99m Tc)-methylenediphosphonate (MDP/MDI)

• Important to evaluate for thepresence of metastatic or multifocaldisease



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Others

• Echocardiography or multiple gatedacquisition scanning: Assess cardiacfunction before, and at various

intervals following, treatment withAdriamycin.



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• Clinical

appearance of ateenager whopresented withosteosarcoma of

the proximal

• Chest

radiograph of patient withosteosarcomawho died from

pulmonary



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• Radiographicappearance

(plainradiograph) of aproximal

humeral

• Intenseradionuclideuptake of the

proximal



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• A comparisonbone scan of the

involvedshoulder (rightimage) with theuninvolvedshoulder (left

• Magneticresonance image

appearance (T1-weighted image)of osteosarcoma

of the proximal

b t



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üLDH

üALP (prognostic significance)

üCBC, including differential

üPlatelet count

üLiver function tests: AST, ALT, bilirubin, andalbumin

üElectrolyte levels: Na+, K+, Cl-, HCO3, Ca2+,Mg2+, P

üRenal function tests: BUN, creatinine

üUrinalysis

boratory

dies

E ki S i



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Enneking Stagingsystem

The key components to the staging systemare the histologic grade of the tumor (lowgrade vs high grade), the anatomic locationof the tumor (intracompartmental vsextracompartmental), and the absence or

presence of metastatic disease. The stagingsystem is typically depicted as follows:Low-grade tumor, intracompartmental – I-ALow-grade tumor, extracompartmental – I-B

High-grade tumor, intracompartmental – II-AHigh-grade tumor, extracompartmental – II-BAny tumor with evidence of metastasis – III



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A compartment may be definedas:

§ any individual bone (ie, eachbone is a compartment untoitself),

§ intra-articular space (ie, apurely intra-articular lesion isintracompartmental), and



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Features of the tumor thatmay impact prognosis

• Stage

– I – low-grade lesions

–

II – high-grade lesions – III – Metastases

• Substage

– A – Intracompartmental lesion(intramedullary lesion for bone tumors)

– B – Extracompartmental lesion

(extramedullary spread for bone tumors)



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• Size of initial tumor

• Histologic response

In a retrospective study by Kim et al, therecords of 331 patients with stage II

osteosarcoma who underwent surgery andchemotherapy were reviewed. The authorsfound that initial tumor size appears to beassociated with histologic response and is

an important prognostic factor in

osteosarcoma.Patients with tumors that have a goodhistologic response (the definition of which

still under debate) to preoperativechemotherapy appear to have a better

prognosis, although this is still under



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Medical Therapy

Before the use of chemotherapy(which began in the 1970s),osteosarcoma was treated primarily

with surgical resection (usuallyamputation).Despite such good localcontrol, more than 80% of patients

subsequently developed recurrentdisease that typically presented aspulmonary metastases. The highrecurrence rate indicates that most

patients have micrometastatic



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• So-called neoadjuvant (preoperative)chemotherapy has been found notonly to facilitate subsequent surgical

removal by causing tumor shrinkagebut also to provide oncologists withan important risk parameter. Patients

in whom there has been a goodhistopathologic response toneoadjuvant chemotherapy (>95%tumor cell kill or necrosis) have a

better prognosis than those whose



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Surgical Indications

The 2 main procedures performed byorthopedic surgeons:

- biopsy

- wide resection

Neither of these proceduresshould be undertaken unlesscomplete tumor staging has

n m l t



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Biopsy

• Biopsy procedures include:

– open biopsy (preferred to avoidsampling error and to provide adequate

tissue for biologic studies),

– trephine biopsy or core needle biopsy(preferred for vertebral bodies and many

pelvic lesions), or – fine needle aspiration (not

recommended).



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Core needlebiopsyinstrumentscommonly usedfor bonyspecimens.Craig needleset.

Close-up view of Craig needlebiopsyinstruments.

Cutting cannulawith T-handleattached (top)and sheaththrough whichthe cutting

cannula passes(bottom).

Resected specimen of a proximal tibiaosteosarcoma. Theprimary lesion was

such that the knee joint was resectedwith the primarylesion. Note that theprevious longitudinalbiopsy tract was

completely excisedwith the specimen.



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Surgical Therapy

• The orthopedic surgeon is of paramount importance in the care of patients with osteosarcoma. Often,

patients thought to haveosteosarcoma are referred to theorthopedic surgeon first to make the

diagnosis. In addition, becauseosteosarcomas are not particularlyresponsive to radiotherapy, surgeryis the only option for definitive

tumor removal (local control).In



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Definitive resection

• The primary aim of definitiveresection is patient survival.

• As such, margins on all sides of thetumor must contain normal tissue(wide margin). The thickness of themargin is important only for the

marrow, where an adequate marginis thought to be 5-7 cm from theedge of an abnormality depicted

on MRI or bone scan.



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• If possible, a number of options existfor limb-salvage reconstruction,which must be chosen based on

individual considerations, as follows: – Autologous bone graft

– Allograft

– Prosthesis

– Rotationplasty



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• Resection of pulmonary nodules:

– wedge resection

–

Lobar resection or pneumonectomy(should be performed at the time of theprimary tumor resection)

– bilateral thoracotomies are

recommended for bilateral disease(each side separated by a few weeks)

• For an osteosarcoma that recurs as

one or more lung lesions only more



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Relative contraindications wouldinclude situations in which the patient

is so frail that the risks of generalanesthesia outweigh any potentialbenefits of surgery. Another relativecontraindication would be a situationin which the atient has extensive

Because osteosarcoma is a deadly form of cancer, no absolute contraindications to

treatment exist.

Contraindications!



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Follow up: Inpatient care

• Further cycles of chemotherapy:generally require inpatient admissionfor administration and monitoring.

Active drugs include: – Methotrexate

– Cisplatin

– Doxorubicin

– Ifosfamide

•

Patients treated with high-dose



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• Fever and neutropenia: Admissionis required for intravenous (IV)antibiotics and monitoring.

• Local control: Admission is requiredperioperatively for local control(surgical resection, amputation),

usually around week 10 of therapy.Resection of metastatic disease (eg,lung nodules) is also performed at

this time.



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Outpatient

• CBC count: done twice each weekfor patients on granulocyte colony-stimulating factor (G-CSF), so that G-

CSF can be discontinued when theabsolute neutrophil count hasreached a predetermined level

(usually 1000 or 5000/ L).μ• Blood chemistries: and liver

function test for patients

on parenteral nutrition or who have



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• Long-term follow-up: Whenpatients have been without therapyfor 5 or more years, they are

considered long-term survivors. These individuals should be seen

annually in a late-effects clinic and

monitored with appropriate studiesdepending on their therapy and sideeffects. Visits may include hormonal,psychosocial, cardiology, and

neurologic evaluations.



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Complications

• Hearing loss is an adverse effect of cisplatin.

• Fever and neutropenia may occur,and if they do, patient admission isrequired for IV antibiotics andmonitoring.

• Patients may require admission for amultitude of other medical problemsduring their chemotherapy treatment

phase, including, but not limited to,



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Outcome and Prognosis

• The overall 5-year survival rate forpatients diagnosed between 1974and 1994 was 63% (59% for males,

70% for females).• Patients with an elevated ALP at

diagnosis are more likely to have

pulmonary metastases.• In patients without metastases, those

with an elevated LDH are less likely

to do well than are those with a



References:

• Harrison’s Principles of InternalMedicine, 17th edition

• Robbins and Cotran’s PathologicBasis of Disease, 7th edition

• Ottaviani G and Jaffe N. 2009. Theepidemiology of Osteosarcoma.Cancer Treat Res. 2009: 152:3-13.

• EMEDICINE

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Osteogenic Sarcoma (Bone tumor)