Tumors of MusculoskeletalJames Pelealu,MD

Definition Neoplasm : abnormal new cell formation, through the rest of life Hereditary mechanism of the cell change irreversible no cell maturity Neoplasm- Primary- Secondary (metastatic)

Incidence Of all tumors : 1,5 % Bone tumors : Benign 65,8% Malignant 34,2 % Most common :

Benign : osteoma (9,3 %), osteochondroma (32,5 %), chondroma (9,8 %) Malignant : Osteosarcoma (48,8 %), GCT (17,5 %), chondrosarcoma (10 %)

CLINICAL MANIFESTATION History :

Px may be completely asymptomatic before x ray findings more likely in benign lession Malignant lession may remain silent if :

Slow growing Pain : common complaint Progressive & unremitting pain sinister symptom, caused by :

Rapid expansion with stretching of surrounding tissues, central haemorrhage or degeneration of tumour

An incipient pathological fracture Tiny lesion

very painful if encapsulated in dense bone Swelling / lump

may be alarming when mass becomes painful / continuous to grow px seeks advice History of trauma

whether the injury initiate pathological changes or merely draws attention unanswered Neurological symptoms (paraesthesia / numbness)

pressure upon or stretching of peripheral nerve Progressive dysfunction

invasion by an aggressive tumour If The lesion is to close to a joint

function disturbed and there may also be painful restriction of joint motion

Osteoma, 39.3

Osteochondroma, 32.5

Chondroma, 9.8

Other Benign Tumors, 18.4

Incidence ofBenign Primary Bone Tumors

Incidence of Malignant Primary Bone Tumors

Osteogenic sarcoma49%

Giant Cell Tumors17%

Chondrosarcoma10%

Other Malignant Tumors

24%

Classification of Neoplasia

Anatomic siteBased on :

Common musculoskeletal tumors

Clinical Presentation

Chief complaint: usually pain, deep seated, dullfirst at night

Age : important clue, certain age group related

Examination Lump

where, discrete / ill-defined, soft / hard, pulsatile, tenderness Swelling

distinguish it from infection or haematoma Near joint

effusion & / limitation of movement Spinal lesions

muscle spasm, back stiffness, painful scoliosis

Physical Examination Examined :

Mass : border, firm or soft, tenderness, pulsating, warm, ruborDD/ with infection or haematoma

Near joint : effusion, limited ROM Spinal lesion : muscle spasm, painful scoliosis Look for metastase : lymph nodes, thyroid glands , prostate, breast

Radiography

Anatomic site : origin of cell Borders

Benign : well define, sclerotic reaction Malignant : ill define, wide transition, min sclerotic

Bone destructiongeographic, moth eaten, permeative

Matrix calcification

Periosteal reaction

Pathological fractureFirst (& only) clinical signInjury was slightElderly people with any break (fracture) of mid-shaft

Watt ( 1985 ) Guideline for ExaminationLesion

multiple / solitary

Type of bone involved

Location in the bone

Margin : well or ill defined

Bony reaction

Calcification

Patterns of Destruction

Geographic

Moth-

eaten

Permeativ

e

Less

malignant

More

malignant

malignancy : non continous, thin, multiple laminationPictures : OsteolisisOsteosclerosisPeriosteal elevation ie. Codmann’s Triangle

Other modalities of Imaging CT Scan hard tissue >> MRI soft tissue >> Bone scan

Laboratory Blood exam : to exclude other cause of lump

infectionmetabolic bone disease

Anemia, elevated ESR, elevated Alk Phospatasenot spesific, help DD/ malignancy

Bence Jones protein in urine Acid phosphatase serum elev in Prostate Ca

Biopsy Needed for diagnosis & treatment planning Needle biopsy

less accurate Open biopsy

small incision, on margin area normal, pseudocapsule, abnormal tissue Benign : excision biopsy Cyst : curretage Performed after imaging exam completed

Staging & Grading Tumour Staging : evaluation of the extent of the tumor at the time of diagnosis Grading : an evaluation of the degree of differentiation Useful for :

- developing evaluation strategies- planning treatment- predicting prognosis

Staging Musculo-skeletal Neoplasms (Enneking) Classification based on:

Histological grade (G) Site (T) Metastases (M)

Enneking staging system was tested retrospectively on 397 cases of bone & soft tissue tumours

The system aids in assessing prognosis & planning management

Surgical Stages

Grading (assessment of biological aggressiveness) 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 metasases G2 High grade malignancy (frequent mitoses, poorly differentiated);

High risk of metasases

Site (anatomic setting of the lesion) T0 Intracapsular T1 Intracompartmental (eg cortical

bone, joint capsule or fascia) T2 Extracompartmental (spreads beyond 'fascial'

plane without longitudinal containment)

Intracompartmental intraosseous intra-articular Intrafascial compartments Extracompartmental soft tissue extension deep fascial extension Extrafascial planes/spaces: (neurovascular containing spaces)

Metastasis (nodal or blood borne tumour spread) M0 No evidence of regional or distant metastases M1 Regional or distant metastases evident

Therapy Remove the lesion minimal risk of recurrence Limb salvage:

Local control of the lesion must be at least to that of amputation surgery The limb that has been saved must functional

Surgical procedure Intralesional Marginal through reactive zone of the tumor WideWith the normal tissue Radical With the compartment

Adjuvant Therapy Chemotherapy Radiation

BENIGN BONE LESIONS Non-Ossifying Fibroma (Fibrous Cortical Defect) Fibrous Dysplasia Osteoid Osteoma Osteoblastoma (giant Osteoid Osteoma) Compact Osteoma (Ivory Exostosis) Chondroma (Enchondroma) Periosteal Chondroma Chondroblastoma Chondromyxoid Fibroma Osteochondroma (Cartilage-Caped Exostosis) Simple Bone Cyst Aneurysmal Bone Cyst Giant-Cell Tumour

Features of aggressive tumours

Eosinophilic Granuloma & Histiocytosis Haemangioma Osteolysis (Disappearing Bones)

Non-Ossifying Fibroma (Fibrous Cortical Defect) Commonest benign lesion of the bone A nest of fibrous tissue persist within the bone before ossifying Asymptomatic usually in children (incidental x-ray finding) Metaphysis of long bone, multiple

X-rayoval radiolucent surrounded by a thin margin of dense bone, adjacent to or within cortex (fibrous cortical defect)

Pathologysolid lesion consist of fibrous tissue, w/ few scattered giant cell

Heal spontaneously (grows), no risk of malignancy Treatment

unnecessary

Fibrous Dysplasia Developmental disorder areas of trabecular bone are replaced by cellular fibrous tissue

containing flecks of osteoid & woven bone Small, single lesion asymptomatic Large, monostotic pain, pathologic # Polyostotic childhood / adolescence w/ pain limp, bony erlargment, deformity, pathologic

# McCune - Albrights Syndrome

Polyostotic disease (unilateral usually) Skin pigmentation cafe au lait spots with serrated borders (called "coast of Maine") that tend to stop

abruptly at the midline of the body Precocious puberty (endocrinopathy) usually presents earlier, may be unilateral or widespread, affecting long bones, hands, feet

& pelvis Malignant transformation (chondrosarcoma or osteosarcoma) is about 4 %;

Treatment:- Small lesion

unnecessary to treat- Big lesion

curetted and grafted -> tendency to recur- Very large lession

the graft can be supplemented by methylmethacrylate cement- With large cysts, the bone often bleeds profusely at operation

Osteoid Osteoma Patients are usually under 30 years old and male predominate The patient complains of persistent pain

Any bone except skull may affected, but over half cases occur in the femur and tibia Px complains : persistent pain localized or referred over wide area WHAT IS OSTEOSARCOMA ?

- A mesenchymally derived, high grade bone sarcoma.- The most common type of cancer that develops in bone.- the third most common malignancy in children and adolescent- the most common age 10-20 years old- Most frequent site near the ends of the long bones :

especially around the knees ( distal femur & proximal tibia ) : ± 80 %proximal humerus

- can develop in any bone ( pelvic, shoulder & jaw )

Non-Ossifying Fibroma (Fibrous Cortical Defect)

X-ray: oval radiolucent surrounded by a thin margin of dense bone, adjacent to or within cortex (fibrous cortical defect)

Fibrous Dysplasia

X-ray: radiolucent ‘cystic’ area in metaphysis or shaft, lucent patches ‘ground glass’ appearance, weight bearing bone bent (shepherd’s crook proximal femur) Scintigraphy : ↑ activity

HOW IS OSTEOSARCOMA DIAGNOSED ?

Signs and Symptoms of Osteosarcoma

Chemotherapy is systemic therapy the drug enters the bloodstream and circulates to reach and destroy the cancer cells throughout the body.

useful for osteosarcoma that has spread through the bloodstream to the lungs and/or other organs.

Most cases of osteosarcoma are treated with chemotherapy given before surgery (neoadjuvant chemotherapy) and after surgery (adjuvant chemotherapy).

SURGERY includes the diagnostic biopsy and the surgical treatment. The surgical treatment can be :

limb-salvage (limb-sparing) surgery (removing the cancer without amputation) or amputation (removing the cancer and all or part of an arm or leg).

EWING’S SARCOMA Arise from endothelial cells in bone marrow Common between the age of 10 – 20 years Usually in tubular bone (tibia, fibula & clavicle) Presents w/ (throbbing) pain & swelling Generalized illness, pyrexia, warm, tender swelling, ↑ ESR suggest osteomyelitis

X-ray: an area of bone destruction (mid-diaphysis)new bone formation extend along the shaft fusiform layer of bone around the lesion ‘onion-peel’ effectalso common ‘sunray appearance’ & Codman’s triangle

Treatmentprognosis poorSurgery little effectRadiotherapy overall survival not enhancedChemotherapy 5-year survival = 50%

Metastastic Bone Disease Age : > decade 5 Pt Bone pain with bone lesion Advanced state Source of skeletal morbidity Common site after lung & liver Secondary bone tumor >> primary bone tumor Site of metastases : vertebrae, pelvic, proximal femur & humerusDefinition A secondary malignant tumor that has spread to the skeleton from a primary carcinoma in an

extraskeletal site Primary of tumor Breast Prostate Kidney GIT Lung

Bone x-ray: Doctors will usually recognize

osteosarcoma on regular x-rays of the bone.

FIGURE 2. Anteroposterior radiograph of a typical mixed sclerotic and lytic osteosarcoma arising from the right proximal humerus in a 16-year-old girl. The tumor has penetrated the bone and formed a soft tissue mass (stage IIB; see Table 4). Note the ossifications in the surrounding soft tissue (arrows).

FIGURE 3. Lateral radiograph of a sclerotic osteosarcoma (arrow) arising in the proximal metaphyseal region of the right tibia in a 16-year-old boy.

EWING’S SARCOMA

Treatment: prognosis poorSurgery little effectRadiotherapy overall survival

not enhancedChemotherapy 5-year survival

= 50%Best

Van Nest Rotasionplasty

Prevalence & IncidencePathophysiology Theory :

Seed & Soil Paget Microenvironmet

Batson venous plexus of vertebrae veins

Types of metastases Based on histopathology Consist of :

OsteollyticOsteoblastic

Osteolytic lesion Bone resosption >> # pathologic Due to :

Direct actionIndirect

release humoral factors Osteoclasts begin to break down bone stimulate tumor cell growth produces substances bone resorption

Osteoblastic Lesion GF stimulate osteoclasts. GF stimulate osteoblasts. Excessive new bone formation Osteoclastic releases GF - tumor cell growth. Osteoblastic releases GF tumor cell growth.

Growth factorsOsteolytic IL-1 IL-6 macrophage inflammatory protein RANKL (receptor activator of nuclear factor κB ligand)Osteoblastic TGF-β BMP Endothelin-1

Osteolytic metastasis

the destruction of bone is mediated by osteoclasts rather than tumor cells. the factors responsible for the activationof osteoclasts vary depending on the tumor.

Osteoblastic metastasis in prostate cancer Overproduction of urokinase-type plasminogen activator (u-PA) by prostate-cancer cells

increases bone metastasis, Bone metastases in prostate cancer are predominantly osteoblastic, with increased numbers

of irregular bone trabeculae. Clinical Feature

Age 50 -70 Advanced cancer Bone lesion in x-ray Symptom :

Prevalence & Incidence

Pain at affected skeletal # pathology ADL Nerve compression Hypercalcemia

Imaging Plain X-ray Bone scintigraphy

Special examination Alkali fosfatase Marker of tumor :

PSA for prostate Management

AIM : Quality of life >> Survival rate >>

Modality : Chemotherapy Radiotherapy Immunotherapy Hormonal therapy

Other :…. Pain control Metastase activity # pathologic Prophylaxis Fixation Spine stability

Bisphosphonates Hypercalcemia of Malignancy most common metabolic complication of malignancy,

www.themegallery.com

CLINICAL USES OF BISPHOSPHONATES

1Hypercalce

mia

of Malignancy

2Bone pain

3Adjunctive Therapy in Metastatic BoneDisease

Focal osteolysis ↑ renal tubular reabsorption of calcium & impaired renal glomerular function,

IV bisphosphonates treatment of choice for hypercalcemia, 70-90% normocalcemia resulting in relief of symptoms and improved quality of life. Use for skeletal metastases from advanced breast cancer. intravenous pamidronate, clodronate, ibandronate, and zoledronate The aim of bisphosphonate treatment to restore the rate of bone resorption to normal.

Bisphosphonates as Adjunctive Therapy in Metastatic BoneDisease First appreciated in the early 1980s, Intravenous infusions of pamidronate, enteric-coated oral pamidronate, or oral or

parenteral clodronate in advanced breast cancer Subsequently a reduction in skeletal morbidity reported in the randomized studies Oral clodronate in advanced breast cancer and multiple myeloma

Action of Bisphosphonat Inhibition osteoclast activity Inhibit proliferation & apoptosis Inhibit ability of adherence & invade ECM Antiangiogenic

Radiofrequency ablation Adjuvant modality P53-induced DNA damage Mineralization of tumor cell Relieve pain