Dr Ranjith Kumar YalamanchiliMS(Ortho)

CLASSIFICATION OF BONE TUMOURS AND GENERAL

PRINCIPLES OF MANAGEMENT

Introduction :

• Neoplasia : It is defined as a mass of tissue formed as result of abnormal, excessive, uncoordinated, autonomous and purposeless proliferation of cells.

• Term Neoplasia includes both Benign and Malignant.

History : • Gross in 1879 presented a paper on sarcoma of long bones where

he has clearly mentioned amputation as the treatment of choice.• Codman in 1926 provided statistical proof of prognosis of

musculoskeletal tumours• Blood Good in 1928 recommended resection and bone

transplantation in order to restore function. He is considered as father of limb sparing surgery.

• In 1930 Radiotherapy came in to light for treatment of metastasis and primary musculoskeletal tumours

• Coley in 1936 attempted chemotherapy using streptococcus pyogenes which he called as TOXIN THERAPY.

• Moore and Bohlman in 1943 introduced Ëndoprosthesis in treating GCT of femur.

FEATURES BENIGN (DIFFERENTIATED) MALIGNANT (UNDIFFERENTIATED)MACROSCOPIC FEATURES

Boundaries Encapsulated or well circumscribed

Poorly circumscribed and irregular

Surrounding tissue Often compressed Usually invaded

Secondary Changes Occur less often Occur more often

MICROSCOPIC FEATURES

Pattern Usually resemble tissue of origin No resemblance

Nucleo – Cytoplasmic Ratio

Normal Increased

Pleomorphism Absent usually Often present

Anisonucleosis Absent Generally present

Hyperchromatism Absent Often present

Growth Rate Usually Slow Rapid

Metastasis Absent Frequently Present

Contrasting Differences between Benign and Malignant Tumours

Routes of Metastasis :• Haematogenous Spread : Most common spread in

musculoskeletal tumours

• Lymphatic Spread – rare in musculoskeletal tumours.• Seen in Rhabdomyosarcoma, Synovial sarcoma, Malignant fibrous

histiocytoma .

• Direct Implantation : – Through surgeons scalpel, needles, sutures, FNAC, diagnostic or excision

biopsy

• Spread through Cerebro Spinal Fluid : – malignant tumours of ependyma and leptomeninges rarely spread

through CSF to vertebrae.

Classification of Tumours

1. WHO Classification : widely accepted and is based on histogenesis

and histological criteria.

2. Classification based on origin of tumours

3. Classification based on site of lesions.

Modified WHO Classification of BONE TUMOURS **** www.springer.de.catalog/nsten/who

• 1. Bone forming tumours :

Benign :OsteomaOsteoid OsteomaOsteoblastoma

IntermediateAggressive

Osteoblastoma

MalignantOsteosarcoma

Conventional osteosarcoma

Telangiectatic osteosarcoma

Juxta cortical or Parosteal

Osteosarcoma

Periosteal Osteosarcoma

2. Cartilage forming Tumours

• BENIGN :• Chondroma• Enchondroma• Osteochondroma• Chondroblastoma• Chondromyxoid fibroma

• MALIGNANT :• Chondrosarcoma• Juxtacortical

chondrosarcoma• Mesenchymal

chondrosarcoma• Clear cell

chondrosarcoma• De differentiated

chondrosarcoma• Malignant

chondroblastoma

3. Giant Cell Tumours :– Osteoclastoma– Malignant giant cell tumour – Giant cell tumour in Pagets disease– GCT occurring in non epithelial region– Giant cell variants : tumors which histologically show the osteoclastic giant cells

1 - aneurysmal bone cyst

2- osteoclastoma

3- chondroblastoma

4- unicameral bone cyst

5- chondromyxoid fibroma

6- non osteogenic fibroma

7- fibrous dysplasia

8- brown tumor of hyperparathyroidism .

4. Marrow tumours

•Ewing sarcoma•Reticulosarcoma•Lymphosarcoma•Myeloma

5. Vascular Tumours– Benign :

» Haemangioma» Lymphangioma» Glomus Tumour

– Intermediate or inderminate variant :» Haemangio endothelioma» Hemangio pericytoma

– Malignant : » Angiosarcoma» Malignant haemangio pericytoma

6. Other Connective tissue tumours• Benign :

» Benign fibrous histiocytoma» Lipoma

• Intermediate : » Desmoplastic fibroma

• Malignant : » Fibrosarcoma» Liposarcoma» Malignant mesenchymoma» Malignant fibrous histiocytoma» Leiomyosarcoma» Undifferentiated sarcoma

7. Other Tumours

• Chordoma• Adamantinoma• Neurilemmoma• Neurofibroma

8. Unclassified Tumours

9. Tumour Like Lesions• Solitary Bone cysts• Aneurysmal bone cyst• Juxta articular bone cyst (Intra osseous ganglion)• Metaphilic fibrous defect ( non ossifying fibroma)• Eosinophilic granuloma• Fibrous dysplasia• Myositis ossificans• Brown Tumour or hyperparathyroidism• Intraosseous epidermoid cyst• Gaint cell granuloma

Classification based on origin of tumours1. Primary Bone tumours : Derived from bone

2. Metastatic bone Tumours : Due to Mets from :

–Breast Lytic + Blastic lesions -Kidney Lytic –Prostate Blastic- Adrenal Lytic –Thyroid Lytic- Intenstine Lytic- Lung, Liver Lytic- Urinary Bladder, Uterine Cervix Lytic lesions

3. Tumour Like Lesions : Non neoplastic Conditions that resemble tumours. Eg : Solitary Bone cyst, Aneurysmal Bone cyst, Fibrous Dysplasia, Brown`s tumour.

Classification based on origin of tumours1. Primary Bone tumours : Derived from bone

2. Metastatic bone Tumours : Due to Mets from :

B –Breast Lytic + Blastic lesions K -Kidney LyticP –Prostate BlasticA- Adrenal LyticT –Thyroid LyticI- Intenstine LyticL- Lung, Liver LyticUniversity - Urinary Bladder, Uterine Cervix Lytic lesions

• {Mnemonic : B.K.PATIL University}

3.

Classification based on site of Origin

1. EpiphysealOsteoclastoma, Chondroblastoma

2. MetaphysealOsteioid osteoma, Osteochondroma, Osteoblastoma, Bone cysts, Osteogenic Sarcoma

3. DiaphysealEwing`s sarcoma, Multiple myeloma,

General Concepts in Tumour Terminology• True Capsule :

• Surrounds a benign lesion and is composed of compressed normal cells and mature fibrous tissue.

• Pseudocapsule : • Compressed tumour cells.

• Fibrovascular zone of reactive tissue with an inflamamtory component that interdigitates with normal tissue and contains satellite lesions.

• Compartment : It refers to bone or muscle of origin; – For Muscle, compartment is that within its Fascia.

– For Bone : • Intracompartmental implies Bone tumour within the

cortex

• Extracompartmental implies a bone tumour that destroys the cortex and spreads in to the surrouding tissue.

• Skip Metastasis :

• A skip metastasis, is defined as a tumor nodule that is located within the same bone as the main tumor or on the opposing side of joint but not in continuity with it.

• High grade sarcomas have the ability to break through the pseudo capsule and metastasize within the same compartment.

– MRI Scan better identifies them.

Satellite lesion Tumour

nodule within reactive zone.

Intra Osseous Skip Mets : Embolization of tumour cells within the marrow sinusoids.

Transarticular Skip Mets : Occur via periarticular venous anastamosis – Very poor prognosis

GRADING and STAGING of TUMOURS• To determine prognosis and choice of treatment.

GRADING : • It is defined as macroscopic and microscopic degree of

differentiation of tumour

• BORDER`s GRADING : – GRADE I : Well differentiated; <25% Anaplastic cells– GRADE II : Moderately Differentiated; 25-50% Anaplastic cells– GRADE III : Moderately differentiated; 50-75% Anaplastic cells– GRADE IV: Poorly differentiated; >75% Anaplastic cells

Enneking`s Grading of Tumours

• G0 Histologically benign (well differentiated and low cell to matrix ratio)

• G1 Low grade malignant – (few mitoses, moderate differentiation and local spread

only); Have low risk of metastases

• G2 High grade malignancy – (frequent mitoses, poorly differentiated); High risk of

metastases

STAGING OF TUMOURS :• STAGING is defined as extent of spread of tumour.

– It is determined by clinical examination, Investigations and pathological studies.

– Common staging systems are

1. ENNEKING `S STAGING SYSTEM

2. AJCC SYSTEM

3. TNM STAGING ( Union International Cancer centre Geneva Staging System )

ENNEKING`s STAGING OF BENIGN TUMOURS

1. Latent—low biological activity; well marginated;often incidental findings (i.e., nonossifying fibroma)

2. Active—symptomatic; limited bone destruction; maypresent with pathological fracture (i.e., aneurysmalbone cyst)

3. Aggressive—aggressive; bone destruction/soft tissueextension; do not respect natural barriers (i.e., giantcell tumor)

• GTM classification described by Enneking is adopted by Musculoskeletal Tumour society and is based on surgical grading (G), location (T), lymphnode involvement & metastasis (M)

Enneking`s :staging of malignant tumours

STAGE GRADE SITE

I A Low – G1 Intracompartmental T1

I B Low – G1 Extracompartmental T2

II A High G2 Intracompartmental T1

II B High G2 Extracompartmental T2

III A Any grade with regional or distal Metastases

Intracompartmental T1

III B Any grade with regional or distal Metastases

Extracompartmental T2

American joint committee on cancer system bone sarcoma classification (AJCC Classification)

The AJCC system for bone sarcomas is based on tumor grade, size, and presence and location of metastases.

TNM STAGING (Union International Cancer centre Geneva Staging System)

• T – Primary Tumour – T0 to T4– In Situ lesion T0 to largest and most extensive T4 primary

tumour

• N – Nodal involvement – N0 to N3– No lymph nodes involvement N0 to wide spread nodal

involvement N3

• M – Metastasis – M0 to M2– No Metastasis M0 to distant metastasis M2

CLINICAL PRESENTATION :• Pain :

– Initially may be activity related, but in case of malignancy there could be progressive pain at rest and at night.

– In benign tumours, pain may be activity related when it is large enough to compress surrounding soft tissue or when it weakens bone.

– A benign Osteioid osteoma may cause night pain initially that classically gets relieved with Aspirin.

• In case of soft tissue sarcomas patients may come with mass rather than pain but in some exceptions like nerve sheath tumours, they have pain and neurological conditions.

• Age : It is the most important denominator because most musculoskeletal tumours occur within specific age ranges.

• Sex : Very few tumours show sex prediliction.• Eg GCT is commoner in females.

• Family History : may be present in tumours like exostosis/ von recklenghausen`s disease.

INVESTIGATIONSSerological investigations :

• 1. Complete Blood Picture :– Haemoglobin : to rule out anaemia that may be due to

replacement of bone marrow by neoplastic process.– ESR : raised in mets, Ewing`s sarcoma, lymphoma,

leukemias• 2. Increased prostate specific antigens with

prostatic acid phosphatase levels in a case of blastic lesions of x ray is the diganostic of Mets secondary to Prostate Carcinoma

3. Serum alkaline phosphatase (ALP) Biological marker of tumour activity. Increases significantly when tumour and metastasis are

highly osteogenic. ALP levels decline after Surgical removal of primary

tumour and elevates if metastasis aggravates. Good prognostic tool.

• Increased in following conditions: - – Osteoblastic bone tumors (metastatic or osteogenic sarcoma)

– 5-Nucleotidase and GGT ( Gamma glutamyl Trasferase ) are elevated in liver pathology along with Alkaline phosphatase, where as in bone pathologies only ALP is increased.

4. Antisarcoma Antibodies : Monoclonal antibodies can be detected by

immunohistochemical assays. Antibodies binding to sarcoma cell surface antigens have

specificity.

5. Osteocalcin – A : Helpful in diagnosing heavily bone producing types of tumours.

6. Serum Calcium : Hypercalcemia is often due to Mets, Myeloma, Hyperparathyroidism.

7. Abnormal Serum protein electrophoresis along with bence jones proteins in urine is classical of Multiple myeloma

Flow Cytometry• A sample of cells are treated with special antibodies

that stick to the cells only if certain substances are present on their surfaces.

• The cells are then passed in front of a laser beam. If the cells now have antibodies attached to them, the laser will cause them to give off light, which can be measured and analyzed by a computer.

• Flow cytometry can help determine type of those abnormal cells and help in diagnosing a tumour early.

INVESTIGATIONS: RADIOGRAPHS

• Phemister's Law = the most common site of infection & tumours is the fastest growing site of the long bone

• To see a lucent lesion in bone, an estimated 30 to 50 % of the bone must first be lost

[Harris & Heaney, N Engl J Med 1969]

Radiographic Evaluation

• Five important parameters in evaluating a tumour on a X RAY are1. Anatomic site 2. Borders 3. Bone destruction 4. New Matrix ( Bone) formation 5. Periosteal reaction

A. Anatomic Sites – X ray

• Anatomic site Specific anatomic sites of the bone give rise to specific groups of lesions.

Characteristic Locations• Simple bone cyst

Proximal humerus• Chondroblastoma

Epiphyses• Giant Cell tumor

Epiphyses• Adamantinoma

Tibia• Chordoma

Sacrum, clivus• Osteoblastoma

Spine, posterior

Characteristic Locations• Simple bone cyst

Proximal humerus

• ChondroblastomaEpiphyses

• Giant Cell tumorEpiphyses

• AdamantinomaTibia

• ChordomaSacrum, clivus

• OsteoblastomaSpine, posterior

• Simple bone cystProximal humerus

• ChondroblastomaEpiphyses

• Giant Cell tumorEpiphyses

• AdamantinomaTibia

• ChordomaSacrum, clivus

• OsteoblastomaSpine, posterior

Characteristic Locations

• Simple bone cystProximal humerus

• ChondroblastomaEpiphyses

• Giant Cell tumorEpiphyses

• AdamantinomaTibia

• ChordomaSacrum, clivus

• OsteoblastomaSpine, posterior

Characteristic Locations

• Simple bone cystProximal humerus

• ChondroblastomaEpiphyses

• Giant Cell tumorEpiphyses

• AdamantinomaTibia

• ChordomaSacrum, Pelvis

• OsteoblastomaSpine, posterior

Characteristic Locations

• Simple bone cystProximal humerus

• ChondroblastomaEpiphyses

• Giant Cell tumorEpiphyses

• AdamantinomaTibia

• ChordomaSacrum, clivus

• OsteoblastomaSpine - posterior

elements

Characteristic Locations

B. Borders• The border reflects the growth rate and the response of the

adjacent normal bone to the tumor.

• Most tumors have a characteristic border

• Benign lesions (e.g., nonossifying fibromas and unicameral bone cysts) have well-defined borders and a narrow transition area that is often associated with a reactive sclerosis.

• Aggressive or benign tumors (e.g., chondroblastoma and GCTs) tend to have faint borders and wide zones of transition with very little sclerosis, reflecting a faster-growing lesion.

• Poorly delineated or absent margins indicate an aggressive or malignant lesion

C. Bone destruction

• Bone destruction is the hallmark of a bone tumor.

• Three patterns of bone destruction are described

1. Geographic, 2. Moth-eaten, 3. Permeative.

Geographic Bone Destruction

Complete destruction of bone from boundary to

normal bone

• Non-ossifying fibroma• Chondromyxoid fibroma• Eosinophilic granuloma

Non-ossifying fibroma

Moth-eaten Bone Destruction• Areas of destruction with

ragged borders• Implies more rapid growth

• Probably a malignancy

Examples:• Myeloma• Metastases• Lymphoma• Ewing’s sarcoma

Multiple Myeloma

Permeative Bone Destruction

• Ill-defined lesion with multiple “worm-holes”• Spreads through marrow space• Wide transition zone• Implies an aggressive malignancy

• Round-cell lesions

Examples:

• Lymphoma, leukemia • Ewing’s Sarcoma• Myeloma• Osteomyelitis• Neuroblastoma

Permeative Bone Destruction

Leukemia

Patterns of Bone Destruction

Geographic Moth-eaten Permeative

Less malignant More malignant

D. Matrix formation• Calcification of the matrix, or new bone formation,

may produce an area of increased density within the lesion.

• Calcification typically appears as flocculent or stippled rings or clusters.

• The appearance of the new bone varies from dense sclerosis that obliterates all evidence of normal trabeculae to small, irregular, circumscribed masses described as "wool" or "clouds."

• Calcification and ossification may appear in the same lesion.

• Neither type of matrix formation is diagnostic of malignancy.

Tumor Matrix

• Osteoblastic

– Fluffy, cotton-like or cloud-like densities

– Osteosarcoma

Cartilaginous : – Comma-shaped,

punctate, annular, popcorn-like

as Enchondroma, chondrosarcoma, chondromyxoid fibroma

Tumor Matrix

Chondrosarcoma

Expansile Lesions of Bone

Multiple myeloma MetsBrown tumorEnchondromaAneurysmal bone cystFibrous dysplasia

Multiple myeloma MetsBrown tumorEnchondromaAneurysmal bone cystFibrous dysplasia

Expansile Lesions of Bone

Renal cell carcinoma

Multiple myeloma MetsBrown tumorEnchondromaAneurysmal bone cystFibrous dysplasia

Expansile Lesions of Bone

Multiple myeloma MetsBrown tumorEnchondromaAneurysmal bone cystFibrous dysplasia

Expansile Lesions of Bone

E. Periosteal reaction

• Periosteal reaction is indicative of malignancy but not pathognomonic of a particular tumor.

• Any widening or irregularity of bone contour may be regarded as periosteal activity.

Solid Periosteal Reactions

Chronic osteomyelitis

• Single solid layer or multiple closely apposed and fused layers of new bone attached to the outer surface of cortex resulting in cortical thickening.

• It is uniterrupted or continous.

Types of Solid Periosteal Reaction

• 1. SOLID BUTRESS• Seen in Aneurysmal bone cyst, chondromyxoid fibroma

• 2. Solid smooth or Elleptical layer• Seen in Osteoid osteoma and osteoblastoma

• 3. Undulating type : • Seen in long standing varicosities, periosteitis, chronic

lymphaoedema.

• 4. Single lamellar reaction :• Seen in Osteomyelitis, Stress Fractures, Langerhans cell

histiocytosis.

Interupted Periosteal Reactions• Commonly seen in

Aggressive/malignant tumours.

– onion-peel ( lamellated)– Ewings sarcoma– Gouchers disease

– Sunburst– Codman’s triangle

Ewing sarcoma

– Sunburst TYPE OF periosteal reaction :

Fine lines of increased density representing newly formed specules of bone radiate laterally from and at right angles to the surface of the shaft giving a typical sun ray appearance.

Osteo-sarcoma

Codman’s triangle :

– When the tumour breaks through the cortex and destroys the newly formed lamellated bone, the remnants of the latter on both ends of the break through area may remain as a triangular structure known as codman triangle.

Also seen in Osteosarcoma, Ewings sarcoma, Chronic Osteomyelitis

Osteo-sarcoma

Periosteal Reactions

Solid onion-peelSunburst Codman’s triangle

Less malignant More malignant

Radiographic Features in a Benign vs. Malignant

Clues by density of lesions

Sclerotic Cortical Lesions

• Osteoid osteoma• Brodie’s abscess

• Osteoid osteoma

• Brodie’s abscess

Sclerotic Cortical Lesions

Mnemonic for Luscent bone lesions = FOGMACHINES

Fibrous DysplasiaOsteoblastomaGiant Cell Tumour Metastasis/ Myeloma Aneurysmal Bone Cyst Chondroblastoma/ Chondromyxoid Fibroma Hyperparathyroidism (brown tumour)/ Haemangioma Infection Non-ossifying Fibroma Eosinophilic Granuloma/ Enchondroma Simple Bone Cyst

• Metastatic lesions– Lung– Renal– Thyroid

• Multiple myeloma• Primary bone tumor

Lytic Lesions in Adults

• Metastatic lesions– Lung– Renal– Thyroid

• Multiple myeloma

• Primary bone tumor

Chondrosarcoma

Lytic Lesions in Adults

• Lymphoma

Blastic Lesions in Children

• Metastatic disease• Breast –female• Prostate –male

• Lymphoma• Paget’s disease• Fluorosis

Prostatic Ca.

Blastic Lesions in Adults

• Metastatic disease• Breast –female• Prostate –male

• Lymphoma• Paget’s disease• Fluorosis

Blastic Lesions in Adults

• Metastatic disease• Breast –female• Prostate –male

• Lymphoma

• Paget’s disease• Fluorosis

Blastic Lesions in Adults

Sled runner tracks in Olliers disease

Mafuccis syndrome – olliers + multiple angiomas

Jail house pattern seen in Haemangioma on X Rays

thickened, vertically oriented trabeculae

Polka dot pattern is seen in cross sections of CT scan.

• It delineates intra and extra osseous extent of tumour.

• It can reliably distinguish between infection and tumor.

• CT scan identifies accurately area of cortical break through, soft tissue extension, medullary spread and proximity of the tumour to neurovascular bundle and evaluating integrity of cortex

• To differentiate solid and cystic lesions.

• Most sensitive investigation to detect Pulmonary mets.

CT scan:-

• Best imaging – to localise the nidus of an osteiod osteoma,– to detect a thin rim of reactive bone around an aneurysmal bone cyst, – to evluate calcification in a suspected cartilagenous lesion and – to evaluate endosteal cortical erosion in a suspected chodrosarcoma.

• To differentiate between the neoplastic mass and inflammatory condition : Neoplastic masses displace soft tissue fat planes where as they are obliterated in inflammatory conditions.

• It cannot differentiate benign from malignant tumours accurately.

• Except in detecting pulmonary mets, Contrast CT is better than plain CT.

• It has better contrast discrimination than any other modality.

• Helps in detecting skip lesions• Assesses the tumor relationship

with adjacent soft tissue, joints and blood vessels.

• It can visualize bone marrow content and demonstrate intramedullary extension of neoplasm.

MRI:-

• It is the investigation of choice in local staging of musculoskeletal tumours.

• On MRI, it is not possible to accurately differentiate benign from malignant tumours. But if the following criteria are present, lesion can be considered as a malignant one :– 1. Mass with irregular Border– 2. Non homogenous signal intensity with extra

compartmental extension– 3. Peri tumoral edematous reaction.– 4. Soft tissue mass situated deep to fascia and measuring

more than 5 cm in greatest diameter is likely to be a sarcoma.

• It uses radioactive glucose to locate cancer by observing high glycolysis rates in a malignant tissue metabolism.

• This glucose contains a radioactive atom that is absorbed by the cancerous cells and then detected by a special receptacle.

• It has low specificity as the FDG ( Fluoro labelled deoxy glucose) can also accumulate in benign aggressive and inflammatory lesions.

• Also helpful in evaluating the tumour after chemotherapy.

• Micromets are better visulaised.

PET- Positron Emission Tomography

Most reliable means of determining vascular anatomy.

• Reactive zone is best seen on early arterial phase, while the intrinsic vascularity is best seen on late venous phase as a tumour blush.

• Transcatheter embolisation is done as a definitive treatment in some benign vascular tumours.

Angiography :

Angiography demonstrating vascularity of a tumour

Embolization of a vascular lesion, performed at least 6 hoursprior to surgery, is expected to significantly reduceintraoperative blood loss.

• Technetium (99mTC) bone scans are used.

• It is an indicator for mineral turnover.

• Whenever there is altered local metabolism in remodeling bone, increased vascularity or mineralization , the isotope uptake is enhanced mainly in reactive zone surrounding the lesions.

• Confirms epiphyseal spread of tumour.

• Helps in detecting multiple lesions like multiple osteochondroma, enchondroma.

• Where as a MRI helps in detecting skip lesions

Nuclear Imaging -Bone scan Scinitigraphy :

Bone scan showing HOT SPOTS over proximal humerus and ribs

It detects the presence of skeletal metastasis and delineates it from primary else where in the body.

• Bone scinitigraphy tends to show larger area of extension of medullary involvement of tumour as the radio active agent also localises the area of hyperemia and edema adjacent to tumour.

• Nuclear imaging is advantageous only to identifying whether skeletal involvement is solitary or multiple.

• Not routinely used in diagnosis of sarcoma; as it better differentiates only bony cystic lesions.

• However Ultrasound is used in guided percutaneous biopsy.

• In patients treated with prosthetic implants, USG is the modality that depicts early recurrence as MRI produces blurred and artifact images due to metallic implants.

Ultrasound:

Used for definitive diagnosis.• Principles of biopsy:

Opted only after all other investigations are performed. A biopsy can be done by FNAC, core needle biopsy, or an open

incisional procedure. FNAC may be 90% accurate at determining malignancy;

however, its accuracy at determining specific tumor type is much lower.

– Trephine or core biopsy is recommended and often yields an adequate sample for diagnosis.

– Complications are greater with incisional biopsy; but least likely to be associated with a sampling error, and provides the sample for additional diagnostic studies, such as cytogenetics and flow cytometry.

Biopsy

– Core biopsy is preferred if limb spraying is an option as it entails less contamination than open biopsy.

– A small incisional biopsy can be performed if core biopsy specimen is inadequate.

– Performed under torniquet (possibly) - the limb may be elevated before inflation but should not be exsanguinated by compression bandage.

Longitudinal incisions preferred as transverse excision are extremely difficult or impossible to excise with the specimen.

NV bundle not exposed. Dissection through muscle (not between) to prevent contamination of tumour.

Approach for open biopsy is made through region of definitive surgical excision. If a drain is used, it should exit in line with the incision so that the drain track also can be easily excised en bloc with the tumor. Wound is closed tightly in layers.

Meticulous haemostasis is arrested by use of bone wax/ Poly Methyl Metha Acrylate(PMMA) to plug the cortical window.

Always sample the tissues from periphery of lesion which contains most viable tissue.

Never biopsy a periosteal reaction / codmans traingle as it contains a new reactive bone and could be false negative.

• If hole must be made in bone during biopsy, defect should be round or oval to minimize stress concentration, which otherwise could lead to pathological fracture. •Torsional strength is not affected by length of defect. Always attempt to keep defects less than 10% of bone diameter.•When biopsy size is greater than 20% of bone diameter, torsional strength decreases to 50%.

Examples of poorly performed biopsies

Biopsy resulted in irregular defect in bone, which led to pathological fracture

Examples of poorly performed biopsies

Transverse incisions should not be used

Needle biopsy track contaminated patellar tendon

Multiple needle tracks contaminate quadriceps tendon

Drain site was not placed in line with incision

Needle track placed posteriorly, location that would be extremely difficult to resect en bloc with tumor if it had proved to be sarcoma

• Biopsy should be done only after clinical, laboratory, and radiographic examinations are complete.

• Completion of the evaluation before biopsy aids in planning the placement of the biopsy incision, helps provide more information leading to a more accurate pathological diagnosis, and avoids artifacts on imaging studies.

• If the results of the evaluation suggest that a primary malignancy is in the differential diagnosis, Biopsy is not done unless it is possible to operate the case in the centre.

Criteria for prophylactic fixation of metastatic tumours of long bones

• Surgical Fixation should not be proceeded until primary neoplasm of bone has been ruled out with biopsy.

• Goals of fixation– maximize ability for immediate mobilization and weight-bearing– protect the entire bone in setting of systemic or metastatic

disease• Type of fixation depends on location of lesion and type of

disease– eg. femur

• cephalomedullary nailing for peritrochanteric lesions • hemiarthroplasty for femoral neck and head lesions

Harington's criteriaof prophylactic fixation

• > 50% destruction of diaphyseal cortices

• > 50-75% destruction of metaphysis (> 2.5 cm)

• Permeative destruction of the subtrochanteric

femoral region

• Persistent pain following irradiation

Mirel`s criteria of fixation

General principles &Technique for En Bloc Tumour excision

Tourniquet

– For fear of embolic expression, exsanguinations of

the extremity is not adviced, instead the limb is

raised for 10 minutes prior to applying the

tourniquet.

Advantages of Tourniquet

• Prevention of tumour embolisation• Ease of distinguishing neoplastic tissue from

normal tissue• Hemostasis of neovasculature• Quicker surgery• More precise resection • No enormous blood transfusion

Incision

• A long vertical incision well above and below the visible limits of the tumour.

• Incision should include the biopsy scar and drain exit tract in an elliptical fashion.

• The plane should be developed through the normal tissues keeping a certain amount of normal tissue surrounding the tumour.

• The main vessel and nerve involvement in tumour mass should be judged and cleared well away from the tumour. If their seperation causes one to enter the reactive zone, this does not become an ideal resection

Wound contamination• Incidence of recurrence is approximately doubled in

case of a wound contamination due to the malignant tissue.

• If contaminated the two options for a surgeon are :– To give up the procedure and consider amputation and

– To meticuously wash the wound to the same fashion as is done for a compound fracture and then proceed with a planned resection.

• Curettage resection and restoration of function by limb salvage procedures or amputation is primary form of surgical correction.

• Based on surgical plane of dissection in relation to tumour, Enneking formulated following types of resection.1) Intralesional Resection2) Marginal resection3) Wide (Intracompartmental) resection4) Radical (Extracompartmental) resection

SURGICAL OPTIONS

• An intralesional margin is one in which the plane of surgical dissection is within the tumor.

• This type of procedure is often described as “debulking” because it leaves behind gross residual tumor.

• This procedure may be appropriate for symptomatic benign lesions when the only surgical alternative would be to sacrifice important anatomical structures.

• This also may be appropriate as a palliative procedure in the setting of metastatic disease.

1) Intralesional Resection :

• As musculoskeletal tumors grow, they compress the surrounding tissues and appear to become encapsulated.

• This surrounding reactive tissue often is referred to as the pseudocapsule.

• Intralesional resection is through the psuedocapsule of the tumor directly in to the lesion. Macroscopic tumour is left behind. Curettage is intralesional proceedure.

CURETTAGE

• Cortical window with rounded margins is made

• When possible, the window is sized larger than the tumour so that the entire tumour is readily seen.

• The rounded margins reduce the risk of subsequent fracture.

• Large curetts should be used to remove the lesional tissue.

Curettage

• Tumour margin should be treated with cryotherapy, PMMA cementage or phenol – alcohol cauterisation, argon beam coagulation in case of aggressive tumours.

• If curettage weakens the bone, graft using allograft or autograft with or with out internal fixation is indicated.

• A marginal margin is achieved when the closest plane of dissection passes through the pseudocapsule.

• This type of margin usually is adequate to treat most benign lesions and some low-grade malignancies.

• In high-grade malignancy, however, the pseudocapsule often contains microscopic foci of disease, or “satellite” lesions.

• A marginal resection often leaves behind microscopic disease that may lead to local recurrence if the remaining tumor cells do not respond to adjuvant chemotherapy or radiation therapy.

2) Marginal Resection :

• Despite an increased risk of local recurrence, a marginal resection may be preferable if the alternative is a more mutilating procedure.

• Improvements in preoperative radiation therapy and neoadjuvant chemotherapy have made marginal resections an acceptable alternative to amputation in some selective circumstances.

• In Marginal resection, dissection passes through the pseudo capsule & reactive zone. Entire structure of origin of tumour is not removed. A margin of atleast 5-7 cm above and below limit of increased bone activity of bone scan is removed.

• Intracompartmental• Wide margins are achieved when the plane of dissection is in

normal tissue.

• Although no specific distance is defined, the Resection includes removal of entire tumour, + Reactive zone & cuff of normal tissue.

• If the plane of dissection touches the pseudocapsule at any point, the margin should be defined as being marginal and not wide.

• Although sometimes impossible to achieve, wide margins are the goal of most procedures for high-grade malignancies.

3) Wide Resection :

4] Radical :- Extracompatmental:

Radical margins are achieved when all the compartments that contain entire tumor and structure or origin of lesion are removed en bloc.

The plane of dissection is beyond the limiting fascial & bone borders.

For deep soft-tissue tumors, this involves removing the entire compartment (or multiple compartments) of any involved muscles.

For bone tumors, this involves removing the entire bone and the compartments of any involved muscles.

Radical operations were previously the procedures of choice for most high-grade neoplasms;

However, with improvements in imaging studies, radical procedures now are rarely performed because equivalent oncological results usually can be obtained with wide margins .

ENNEKING`s Classification of Surgical Procedures for Bone Tumors

Margin Local (Mode of resection)LIMB SALVAGE OPTIONS

Amputation(Mode of amputation)

Intralesional Curettage or debulking

Debulking amputation

Marginal Marginal excision Marginal amputation

Wide Wide local excision Wide through bone, amputation

Radical Radical local resection

Radical disarticulation

Enneking`s Classification of Resection of tumours.

1] Limb Salvage Proceedures

2] Amputations

SURGICAL OPTIONS:

• It is designed to accomplish removal of a malignant tumour & reconstruction of the limb with an acceptable oncologic, functional & cosmetic result.

• It is sub amputative wide resection with preservation of the limb & its function.

Indications : Stage IA Stage IIA & Stage IIIA (All intracompartmental

tumours)with good response to pre-operative chemotherapy Skin should be uninvolved and free There should be feasibility of keeping a cuff of normal tissue

surrounding the tumour Upper extremity lesions are more suitable for limb sparing surgery Tumours with good pre-operative chemotherapy response

Limb salvage procedures

Advantages of limb salvage proceedures :• long term survival rates of patients have improved from

approximately 20% to 70%.

• The function of the salvaged limb is better than that of the amputation but not normal function.

Limb salvage procedures vs Amputation

Disadvantages of limb salvage proceedures:

Limb salvage is more extensive procedure with greater risk of infection, wound dehiscence, flap necrosis, blood loss & DVT.

More chances to undergo multiple future operations for the treatment of complications.

After initial salvage upto 33% of long term survivors may ultimately require an amputation.

Limb salvage procedures vs Amputation

Guidelines: No major neurovascular tumour involvement.Wide resection of the affected bone with normal

muscle cuff in all directions.Enbloc removal of all previous biopsy sites & all

potentially contaminated tissues.Resection of bone 3-4 cms beyond abnormal uptake

as determined by CT /MRI /BONE SCAN.Resection of the adjacent joint & capsuleAdequate motor reconstruction &soft tissue

coverage.

Limb salvage procedures

1. Major neurovascular involvement.

2. Pathological fractures spread tumour cells through fracture hematoma increasing risk of recurrence.

3. Inappropriate biopsy sites contaminate normal tissue planes and jeopardizes local tumour control.

4. Infection flares with metallic implants and thereby jeopardises effect of chemotherapy..

5. Skeletal immaturity : Predicted limb length discrepency should not be >6-8cm. In such cases expandable prosthesis be used. Upper limbreconstruction is independent of skeletal maturity.

6. Extensive muscle involvement.

Contraindications: Limb salvage procedures

1. Resection of the tumourTo avoid local recurrence.

2. Skeletal reconstructionTechnique of reconstruction is independent of resection.

3. Soft tissue & muscle transfers.To cover and close resection site and to restore motor power. Distal tissue transfers not used for possibility of contamination.

Stages of Limb salvage procedures

• Reconstruction of bone defect may be done by

1] Osteoarticular allograft reconstruction2] Allograft-prosthesis composite

reconstruction 3] Endoprosthetic reconstruction. 4] Allograft arthrodesis

5} Rotationplasty6} Turnoplasty

Surgical reconstructive options :

• Possibility to replace ligaments, tendons & intraarticular structures

• Osteoarticular allografts may have a role as a temporary measure to preserve an adjacent physis in an immature patient, when the alternatives include amputation or sacrifice of both physes.

• A proximal tibial osteoarticular allograft could be used in an immature patient in an attempt to preserve the distal femoral physis until skeletal maturity.

• This could be converted later to an endoprosthetic reconstruction when it becomes necessary

• Complications :-non-union at graft –host junction, fatiguefracture ,articular collapse, degenerative joint disease

1. Osteoarticular allograft reconstruction:

2.Allograft-prosthesis composite reconstruction:

Main indication for an allograft-prosthesis composite is an inadequate length of remaining host bone to secure the stem of an endoprosthesis. Tumor prosthesis is used for reconstruction with allograft for fixation to the remaining host bone. Case scenario : osteosarcoma of `proximal humerus.

X ray shows tumor extending down to distal diaphysis.

Intraoperative photograph after wide resection of tumour.

Humeral allograft is prepared to accept stem of tumor prosthesis

Allograft is fixed to bone with medial and lateral plates.

Prosthesis is cemented into allograft.

Postoperative radiograph.

• It also provide long-term function for some patients.

• Endoprosthetic reconstruction provides the advantage of predictable immediate stability that allows for quicker rehabilitation with immediate full weight bearing.

• Most endoprostheses are modular, allowing for incremental limb lengthening as an immature patient grows.

3.Endoprosthetic Reconstruction:

• Polyethylene wear is still a limiting factor for articulating surfaces, but the inserts are easily replaceable in most prostheses.

• Fatigue fracture can occur at the rotating hinge.

• Fatigue fracture at the base of the intramedullary stem where it attaches to the body of the prosthesis is more problematic. In this location, extraction of the remaining stem can be extremely difficult.

4. Resection Arthrodesis – Ennekings shirney

5. ROTATIONPLASTY :

Winkelmann classified ROTATIONPLASTYinto five groups, as follows:

1. Group AI– Lesion in distal femur. – The distal femur, knee joint, and proximal tibia are resected; the lower leg is rotated 180 degrees; and the tibia is joined to the remaining femur.

Rotationplasty :

• The distalmost femur, knee joint, and proximal tibia are resected. After rotation of 180 degrees, the distal tibia is joined to the distal femur.

2. Group AII—Lesion in the proximal tibia.

• The upper femur and hip joint are resected, and the leg is rotated180 degrees. The distal femur is joined to the pelvis so that the knee functions as the hip, and the ankle functions as the knee.

3. Group BI—Lesion in the proximal femur sparing the hip joint and gluteal muscles

• The upper femur, hip joint, and lower hemipelvis are resected, and the leg is rotated 180 degrees. The remaining femur is joined to the remnant of the ilium so that the knee functions as a hinged hip joint and the ankle functions as the knee.

4. Group BII—Lesion in the proximal femur with involvement of hip joint and contiguous soft tissue

• The entire femur is resected. • The tibia is attached to the pelvis using an

endoprosthesis.

5. Group BIII—Lesion in the mid Femur

• "TuRN-up PLAsTy" of the tibia refers to the replacement of a femur by substituting the iniverted tibia and fibula. This procedure has been utilized to avoid total ablation of a lower extremity and to provide a thigh stump for a prosthesis.

• A metallic hip prosthesis is used at turned up end of the tibia.

• The first description of the operation was by Sauerbruch in 1922. His first case was a girl of 13 years with an ununited fracture of the femur with chronic osteomyelitis and considerable loss of substance of the shaft in which he did a resection of the femur distal to the trochanters and attached the distal tibia to it.

6. Turn-up-plasty *** :*** Anals of Orthopaedic Surgery, Total Resection of Femur with "Turn-up Plasty" of Tibia and Prosthetic Replacement of Hip Joint; HENRY S.

WIEDER, JR., M.D., JESSE T

Two types of prosthesis are used:• 1. modular

• 2. custom made

7. PROSTHETIC ARTHROPLASTY

Custom made prosthesis to accomodate large proximal femoral defects after resection

• A tailor- made metallic prosthesis for a particular patient with specific measurements is called custom prosthesis.

• Designed using 3D computer modeling & CAD – CAM technologies.( Computer Assisted Designs and computer assisted manufacturing )

Custom mega prosthesis

• For pediatric patients, future limb-length inequality must be considered.

• For patients who are near skeletal maturity, the reconstructed limb can be lengthened 1 cm at the initial procedure.

• Also, epiphysiodesis of the contralateral limb can be done at the appropriate age to preserve limb-length equality (or to minimize inequality).

• For younger patients, however, other options should be considered.

• Although amputation and rotationplasty were previously considered the only reasonable treatments for very young patients with bone sarcomas, use of expandable prostheses currently is gaining support.

Paediatric Consideration:

• The surgical technique, postoperative course, rehabilitation, function, and complications for implantation of this device is similar to that of other endoprostheses .

• The device is unique, however, in that it uses energy stored in a compressed spring to allow for future expansion of the prosthesis as the child grows.

Repiphysis Expandable Prosthesis

Electromagnetic expansion of Repiphysis expandable prosthesis.

• Amputation provides definitive surgical treatment when limb sparing is not a prudent one.

• Common amputations in malignant tumours:

– Proximal humerus : fore quarter amputation– Distal femur : hip disarticulation– Proximal tibia : mid thigh amputation

AMPUTATIONS :

Ennekings Classification of Amputations

• Levels of Above knee

amputation :

• Adjuvant chemotherapy:– To treat presumed micrometastasis

• Neo adjuvant[induction]– Before surgical resection of the primary tumour

Advantages:– It controls micro metastasis and improves survival rate.– Chemotherapy makes limb salvage surgery easier.– Decreases tumor size and vascularity.– The response to Chemotherapy can be evaluated after surgery.

Chemotherapy

• Here the chemotherapy is intituted after the primary tumour has been controlled by alternative treatment such as surgery or radiotherapy.

• The rationale is the microscopic metastatic disease can be eradicated.

• Majority of the regimen used is High Dose Methotrexate.

Adjuvant chemotherapy

• Chemotherapy that is given before local resection is considered neoadjuvant chemotherapy.

• The most common reason for neoadjuvant therapy is to reduce the size of the tumor so as to facilitate more effective surgery.

Neoadjuvant therapy

Neoadjuvant chemotherapy

Advantages Disadvantages• Early institution of systemic

therapy against micrometastases

• Less chance of drug resistant clones

• Reduces tumour size sparing limb salvage chances

• Less chance of spread of viable tumour during surgery

• Delays definitive control of bulk disease and chances for systemic dissemination.

• Risk of local tumour progression with loss of limb sparing option

• Psychological effect of retaining tumour

Adjuvant chemotherapy

Advantages Disadvantages• Removal of bulk tumour

decreases tumour burden and increases growth rate of residual disease making s-phase specific agents more active.

• Decreased probability of selecting drug resistant clone in primary tumour.

• Dealy of systemic therapy for micrometastases.

• Possible spread of tumour by surgical manipulation.

• No preoperative in vivo assay of cytotoxic response.

GRADE EFFECT

I Little or No response of tumour identified

II Areas of necrosis and tumour cells seen.

III Scattered foci of tumour cells seen.

IV No Tumour cells seen.

HUVO`s Histologic grading of effect of preoperative chemotherapy on primary Bone tumour

GRADE EFFECT I No viable tumour cells

II Single tumour cells or clusters <0.5cm

III Viable tumour cells <10%

IV Viable tumour cells 10-50%

V Viable tumour cells >50%

VI No response

Salzer-Kuntschik `s Histologic grading of effect of preoperative chemotherapy on primary Bone tumour

• With Megavoltage radiotherapy tumor cell can be destroyed.

• High voltages are administered in short sessions.

• Radiation therapy should be started immediately after diagnosis before surgery to prevent metastasis .

• Chemotherapy increases the susceptibility of tissues to irradaition.

• Protect all normal tissue biopsy scars to prevent radiation

necrosis.

• Distribute the dose in accordance with distribution of tumor.

RADIOTHERAPY

Diagnosis

Neoadjuvant chemotherapy + Radiation

Resection/ surgery Repeat Chemo + Radiation

Adjuvant + irradiation +chemo Histological Grading

Sequence of treatment:

Gene therapy in sarcomas :• Targeting Osteocalcin promoter.• Osteocalcin is produced both in Osteoblastic[100%]and fibroblastic[70%]

Osteosarcoma.

LIQUID BRACHYTHERAPY : – Injecting Intra arterial infusion of chemotherapeutic drugs with

brachytherapy – It is in Phase 2 trials currently.

• Cryotherapy is used in curettage after resection of primary tumour to prevent chances of recurrence.

• PMMA, Phenol, liquid nitorgen commonly used cryoprecipitates.

Recent advances

Internal or Sealed source chemotherapy.

• Brachy means close/short distance.

• Source is placed near to the target tissue through multiple catheters placed over tumour bed.

• High dose can be delivered to the target tissue..with minimal side effects.

Brachy therapy:

• A portion of tumour is implanted in to a sarcoma survivor and removed after 14 days.

• Sensitized lymphocytes from survivors are infused in to patient. These cells selectively kill the cancer cells.

Immunotherapy

Extracorporeal Irradiation

• En-bloc resection, extracorporeal irradiation, and re-implantation is done in limb salvage for bony malignancies.

• After en-bloc resection, the segment is wrapped in a wet sterile drape to minimise air gaps, placed in two sealed sterile plastic bags and wrapped in another sterile drape.

• This is delivered for radiotherapy.

Extracorporeal Irradiation

• Meanwhile, the operative site is prepared for re-implantation and marginal biopsies taken.

• On return the specimen is removed from the inner plastic bag and soaked in iodine solution.

• It is cleared of unnecessary soft tissue leaving important muscle insertions for re-attachment and then re-implanted

Cementoplasty • Patients with osteolytic tumours (metastasis, multiple

myeloma, lymphoma) located to the vertebral body, acetabulum and condyles and causing local pain, disability and with a risk of compression fracture are excellent indications.

• Used in cases of palliative care to stabilise the lytic lesion.• For vertebroplasty, a 10-G and 15-G beveled needle (for

thoracic/lumbar and cervical level, respectively) should be used.

• Cement injection should be done under real-time imaging.

LASER ABLATION for Benign Tumours

• Because of the small size of the ablation zone produced, laser is mostly used for small tumours or in case of Radio frequency contraindications (metallic implants).

• Osteoid osteomas are the best indication.

• The laser fibre (400 to 600 µm) is inserted always coaxially into the tumour under CT-guidance through a spinal needle and a laser beam directed to ablate the tumour.

Direct intra arterial chemotherapy

• Usually in chemotherapy is given intra venously, but direct intra arterial administration there by localising the drug more pertaining to the affected tumour gives better results.

ISOLATED LIMB PERFUSION METHOD

Effective way of delivering chemotherapy to the affected limb alone reducing systemic side effects.

With a steinmann pin over iliac bone to anchor Eschmark torniquet in order to occlude proximal blood vessels.

Cannulation of vessels and delivering the drug by ensuing warmth and perfusion of the limb.

Oncologist BoneTumoursDiagnosisTreatment

Radiologist

CytopathologistSurgeon

HistopathologistMolecular

PathologistGeneticist

psychiatrist

NursingAnd

Support staff

Audit

MUSCULOSKELETAL TUMOURS are Evolving in to a multi disciplinary approach

References :

• Campbell’s Operative Orthopaedics – 11th & 12th edition• Samuel Turek Text Book of Orthopaedics: 2nd edition• Bone and Cancer: Felix Bronner • Adam Greenspan- Differential diagnosis in orthopaedic oncology, 2nd edition• Mercers Orthopaedic Surgery Vol II 9th edition and 11th edition• WHO Manual 2001 reprint for Classification of Musculoskeletal Tumours • Wheeless`Textbook of Orthopaedics.• www.uptodate.com/musculoskeletal tumours • Anals of Orthopaedic Surgery, Total Resection of Femur with "Turn-up Plasty" of

Tibia and Prosthetic Replacement of Hip Joint; HENRY S. WIEDER, JR., M.D., JESSE T • Musculoskeletal cancer surgeries – treatment of sarcomas and allied diseases –

Martin M. Malawer• American Academy of Orthopaedic Surgeons – Text book of Orthopaedic

knowledge update 8 series.

THANK YOU

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trabeculae)• Jail House appearance X ray finding in a haemangioma

(thickened, vertically oriented trabeculae• Double density Sign Osteioid Osteoma – Bone scan feature