An Approach to Malignant Bone Tumors

Dr.Suhas B MD Radio-Diagnosis

Introduction• Bone tumors are classified into:

– Primary bone tumors– Secondary bone tumors ( Metastasis)

• Most are classified according to the no rm a l c e ll o f o rig inno rm a l c e ll o f o rig in and apparent pattern of differentiation.

• Forms 0.2% of human tumor burden.

• Primary malignant bone tumors make 1% of all malignant tumors.

• Commonest bone tumour is secondaries from other sites.

• Commonest primary bone tumour is multiple myeloma, second osteosarcoma.

Occurence

Classification

• Bone-forming tumours• Cartilage forming tumours• Giant-cell tumour• Marrow tumours• Vascular tumours• Other connective tissue tumours• Other tumours• Secondary malignant tumours of bone

Bone-forming tumors (malignant)

Osteosarcoma• Central (medullary)• Peripheral (surface) Paraosteal Periosteal High grade surface

Cartilage-forming tumors (malignant)

Chondrosarcoma• Differentiated chondrosarcoma• Juxta-cortical chondrosarcoma• Mesenchymal chondrosarcoma• Clear cell chondrosarcoma

Marrow tumors (malignant) Ewing’s sarcoma Neuroectodermal tumour Malignant lymphoma of bone

(Primary/secondary) Myeloma

Vascular tumors (malignant) Angiosarcoma Malignant haemangio

pericytoma

Other tumors (malignant) Chordoma Adamantinoma

Other connective tissue tumours (malignant)

Fibrosarcoma Malignant fibrous

histiocytoma Liposarcoma Malignant mesenchymoma Leiomyosarcoma Undifferentiated sarcoma

Secondary malignant tumours of bone

Osteoblastic Osteolytic Mixed Lesions

Evaluation

• Age & Sex

• Symptomatology– Pain– Swelling– History of trauma– Neurological symptoms– Restriction of movement– Other constitutional sympotms (cough, chest pain, backache, loss of

appetite etc)

• Pathological fracture• Associated conditions• Prior surgeries/investigations

Age distribution of various bone tumors

Imaging

• Plain radiography

• CT scan

• MRI

• Radionuclide scanning

• PET

Plain Radiography

Information yielded by radiography includes :

• Size• Site of the Lesion• Borders of the lesion/zone of transition • Type of bone destruction • Periosteal reaction• Matrix of the lesion • Nature and extent of soft tissue involvement • Multiplicity

Plain radiography (contd.)

Size• It helps us in pre treatment staging of the tumor.• The larger the lesion the more likely to be

aggressive or malignant.

Plain radiography (contd.)

Site

• Type of bone • Long bone / Flat bone • Intramedullary /

Eccentric / Cortical lesion

• The epicenter of the tumor helps to determine the origin.

• Epiphysis / Metaphysis / Diaphysis

Distribution of various bone tumors

Distribution of various lesions in a long tubular bone before skeletal maturity

Distribution of various lesions in a long tubular bone after skeletal maturity

Distribution of various lesions in a vertebra

Benign lesions predominate in its posterior elements.

Osteoblastoma Osteoid osteoma Aneurysmal Bone

cyst Osteochondroma Chondromyxoid

fibroma

Malignant lesions are seen predominantly in its anterior part (body)

Lympohoma Myeloma Osteosarcoma Ewing

Chondrosarcoma Metastases

Zone of Transition • The zone of transition is the most reliable indicator in determining whether

an osteolytic lesion is benign or malignant.

• The zone of transition only applies to osteolytic lesions since sclerotic lesions usually have a narrow transition zone.

• A small zone of transition results in a sharp, well-defined border and is a sign of slow growth. A sclerotic border especially indicates poor biological activity.

• An ill-defined border with a broad zone of transition is a sign of aggressive growth.

Narrow zone of transition Wide zone of transition

Patterns of Bone Destruction

• Mechanisms of bone destruction– Direct effect of tumor cells – Increased osteoclastic activity

• Cortical bone is destroyed less rapidly than trabecular bone. – Loss of cortical bone appears earlier on radiography – trabecular bone must be destroyed (about 70% loss of mineral

content) before the loss becomes radiographically evident

• Bone destruction can be described as – geographic (type I) - benign lesions– moth-eaten (type II) and– permeative (type III) - rapidly growing infiltrating tumors

Patterns of Destruction

Less malignant More malignant

Geographic Moth-eaten Permeative

Types of Periosteal reaction

• Benign– None– Solid/Continuous

• More aggressive or malignant Interrupted– Lamellated or onion-

skinning– Sunburst– Codman’s triangle

Periosteal Reactions

Less malignant More malignant

Solid Sunburst

Codman's Triangle

Lamellated

C. by the presence of a solid sclerotic mass, such as in parosteal osteosarcoma

Types of matrix: osteoblastic

A. fluffy, cotton-like densities within the medullary cavity, e.g in this case of osteosarcoma of the distal femur

B. presence of the wisps of tumor-bone formation, like in this case of osteosarcoma of the sacrum

The matrix of a typical osteoblastic lesion is characterized by the presence of the following features :

Types of matrix: chondroid matrix A: Schematic representation of various appearances of chondroid matrix calcifications.

B: Enchondroma displays a typical chondroid matrix

C: Chondrosarcoma with characteristic chondroid matrix

Radiographic features differentiating primary soft tissue tumor invading bone from primary bone tumor invading soft tissues

Radiographic features that may help differentiate benign from malignant lesions

CT• Features are similar to that of plain radiograph, however CT scanning may be

helpful locally when the radiographic appearances are confusing, particularly in areas of complex anatomy.

• Very useful in early diagnosis.

• Cross-sectional images provide a clearer indication of bone destruction, as well as the extent of any soft tissue mass, than the radiographs.

• CT scanning may depict small amounts of mineralized osseous matrix not seen on radiographs.

• The modality may be particularly helpful in visualizing flat bones, in which periosteal changes may be more difficult to appreciate.

• Early detection of pulmonary secondaries

• Exact measurement for limb salvage procedures (Prosthesis/allograft)

• Used for prognostic follow-up of the patient.

MRI• Investigation of choice to assess intra-medullary extension and soft

tissue involvement.• Defines the relationship to the nearby neurovascular bundles.• Ambiguous and inconspicuous cases.• Helps in staging of the tumor and to plan its surgical management.

Radio-nuclide bone scan• For pre biopsy staging• Dissemination of tumour• Silent secondaries and skip lesions

Arteriogram• Planning limb sparing surgery• Therapeutic embolization• To assess vascularity of tumour

Osteosarcoma • Osteosarcoma is a primary bone-producing

malignant mesenchymal tumor.

• It is the most common primary malignant tumor of bone, excluding plasma cell myeloma.

• Osteosarcoma represents 20% of all primary malignant bone tumors.

• Osteosarcoma is encountered most commonly in the age group from 10 to 25 years (75% of cases); few cases occur before age 5 or after age 30.

• M:F=2:1• The metaphyseal lesion abutting the physis is the

classic location in 75% of cases.

• Although usually in the long bones, may occur in other places:

Craniofacial Small bones Extraskeletal (soft tissue)

Associations - Irradiation, Pagets disease, Rothmund-Thompson syndrome

Osteosarcoma (contd.)

Radiography

Conventional Radiography• medullary and cortical bone

destruction• wide zone of transition,

permeative or moth-eaten appearance

• aggressive periosteal reaction

• sunburst type• Codman triangle• lamellated (onion skin)

reaction: less frequently seen

• soft-tissue mass• tumour matrix

ossification/calcification• variable: reflects a

combination of the amount of tumour bone production, calcified matrix, and osteoid

• ill-defined "fluffy" or "cloud-like" cf. to the rings and arcs of chondroid lesions

Osteosarcoma (contd.)

CT • Cross-sectional images provide a clearer

indication of bone destruction, as well as the extent of any soft tissue mass, than do radiographs.

• CT scanning may depict small amounts of mineralized osseous matrix not seen on radiographs. The modality may be particularly helpful in visualizing flat bones, in which periosteal changes may be more difficult to appreciate

Osteosarcoma (contd.)

MRIT1WI - Low/heterogenous signal intensityT2WI - High signal intensityConstrast - enhancing medullary cavity and solid

components.STIR - High signal intensity and helps in

assessing involvement of neurovascular bundles and muscles.

Multiple Myeloma• Multiple myeloma is the most

common primary malignant neoplasm of the skeletal system. The disease is a malignancy of plasma cells.

• Average age is 60-70

• Much more common in men than women

• Most have an elevated serum protein with 80-90% in the globulin fraction, especially IgG

• Bence-Jones protein in 40-60% of patients

• Most commonly affected bones are: vertebrae (66%), ribs (45%), skull (40)%, shoulder (40%), pelvis (30%), and long bones (25%).

Multiple Myeloma (contd.)Plain Radiography• A full skeletal survey is required for proper

evaluation.

• No. of lytic lesions is directly proportional to the tumor load.

• Classical lesions are well defined rounded/punched out lytic lesions scattered diffusely among the involved bones.

• Such lesions in skull gives 'pepper pot' or 'swiss cheese' appearance, however the occipital bone is spared.

• Multiple deformed vertebral bodies.

• Diffuse osteopenia

• No periosteal bone formation.

• Medullary involvement in the form of endosteal scalloping.

Multiple Myeloma (contd.)CT• Computed tomography (CT) scanning readily

depicts osseous involvement in myeloma.

• CT allowed a more accurate evaluation of areas at risk of fracture.

• Tool of choice utilised in image guided spinal or pelvic bone biopsy.

MRI• Most sensitive imaging modality at detecting

diffuse and focal multiple myeloma in the spine, as well as the extra-axial skeleton

• Mainly bone marrow based lesions.

• T1WI - Low signal intensity

• T2WI and STIR - High signal intensity.

• Show enhancement on contrast enhanced images.

Chondrosarcoma• malignant cartilaginous tumour and

second most frequent primary malignant tumor of bone, representing approximately 25% of all primary osseous neoplasms.

• Typical presentation is in the 4th and 5th decades and there is a slight male predominance

• Further differentiated into Primary and secondary

• Most common bones involved are long bones (45%), pelvis (25%), ribs (8%), spine (7%), scapula (5%), sternum (2%)

• Patients with multiple enchondromas like in Ollier's disease and Mafucci's syndrome are at risk.

Chondrosarcoma (contd.)Plain radiography• large mass at the time of diagnosis,

usually over 4 cm in diameter in 50% of cases.

• lytic (50%)

• intralesional calcification(s): 60-78% (rings and arcs calcification or popcorn calcification)

• endosteal scalloping

• affects more than two thirds of the cortical thickness (c.f. less than 2/3 in enchondromas)

• moth eaten appearance or permeative appearance in higher grade tumours

• cortical remodelling, thickening and periosteal reaction are also useful in distinguishing between an enchondroma and low grade chondrosarcoma

Chondrosarcoma (contd.)CT• In as many as 90% of cases, tumors

appear as lucent areas containing chondroid matrix calcification. Endosteal scalloping and cortical destruction are frequently easier to appreciate on CT scans than on radiographs.

• CT scanning may be used to guide percutaneous biopsy

MRI• T1: low to intermediate signal

• T2: very high intensity in non mineralised/calcified portions

• gradient echo/SWI: blooming of mineralised/calcified portions

T1 C+ (Gd) • most demonstrate heterogeneous

moderate to intense contrast enhancement.

• enhancement can be septal and peripheral rim-like corresponding to fibrovascular septation between lobules of hyaline cartilage

Ewings Sarcoma• Ewing sarcoma, a highly malignant

primary bone tumor that is derived from red bone marrow and second most common primary bone tumour of childhood.

• This tumor is most frequently observed in children and adolescents aged 4-15 years and rarely develops in adults older than 30 years.

• Affected bones include, long bones: 50-60%, femur: 25%, tibia: 11%, humerus: 10%, flat bones: 40%, pelvis: 14%, scapula, ribs: 6%

• As far as location within long bones, the tumor is almost always metaphyseal or diaphyseal.

• It is the most lethal bone tumor. An association exists between Ewing sarcoma and primitive peripheral neuroectodermal tumor (PNET).

Ewing's Sarcoma (contd.)

Plain Radiography• Typical presentation: ill-defined

osteolytic lesion with a moth-eaten or permeative type of bone destruction, irregular cortical destruction and aggressive periostitis.

• reactive sclerosis, irregular periosteal reaction and soft tissue mass.

• Ewing sarcomas tend to be large poorly marginated tumours, with over 80% demonstrating extension into adjacent soft tissues.

• laminated (onion skin) periosteal reaction: 57%

Ewings Sarcoma (contd.)CT• CT scanning helps to define the bone

destruction that is associated with Ewing sarcoma.

• Tumor size can be evaluated with contrast-enhanced CT scanning, which may be used in follow-up evaluation during chemotherapy.

MRI• MRI is essential to elucidate soft-

tissue involvement

• T1: low to intermediate signal• T1 C+ (Gd): heterogeneous but

prominent enhancement• T2: heterogeneously high signal, may

see hair on end low signal striations

Lymphoma• Primary lymphoma of bone (PLB) is a rare,

malignant, neoplastic disorder of the skeleton. Also known as Reticulum cell sarcoma.

• Primary bone lymphoma occurs in a broad range of patients, aged 1 year 6 months to 86 years (median range, 36–52 years) (5), with a peak prevalence among patients in the 6th to 7th decades of life.

• Presentation: usually pain and palpable mass.

• Preferential sites: femur, tibia, humerus and iliac bone.

Plain Radiography The features vary widely in appearance.

The most common ones are as below : Permeative, lytic pattern of bone

destruction (74%) Metadiaphyseal location (69%) Periosteal reaction (58%) Soft-tissue mass (80-100%)

Lymphoma (contd.)CT• useful adjuncts to conventional

radiographs

• pattern appears as extensive evidence of disease within the marrow cavity associated with a surrounding soft-tissue mass but without extensive cortical destruction

• Cortical breakthrough is well appreciated.

MRI• T1WI - low signal intensity within the

marrow

• T2WI - High signal intensity

• Contrast - diffuse heterogenous/homogenous enhancement

Adamantinoma• rare primary malignant bony tumour, only

approximately 200 cases have been reported.

• The tumor occurs almost exclusively in the long bones; tumors in the tibia account for more than 80% of cases. The diaphyseal region is the area most commonly affected. Other bones affected are the jaw, ulna, humerus, femur, and fibula.

• Typically presents in the 2nd to 3rd decades as a locally aggressive mass 3-15 cm in diameter.

• Differentiated <20 years of age> Classic• 10-year survival rate is believed to be 10%• Adamantinoma may present as a solitary

focus or multicentric lucencies or slightly expansile osteolytic lesion

• May extend into the marrow cavity.• Lesions tend to have an eccentric

epicenter and a lack of periosteal reaction.• usually no periosteal reaction is noted in

the surrounding bone• Long-standing tumors produce marked

cortical thickening and spool-shaped bulges of the outer cortex in an eggshell fashion.

AdamantinomaMRI• two morphologic patterns are seen : - a solitary lobulated focus - multiple small nodules in one or

more foci.

• In some patients separated tumour foci may be seen, defined as foci of high signal intensity on either T2- or T1-weighted contrast-enhanced images, interspersed with normal-appearing cortical or spongious bone.

• Fluid-fluid level may occasionally be seen.

• C+(Gd): tends to show intense and homogeneous static enhancement, although there is no uniform dynamic enhancement pattern.

Metastases• Metastatic bone tumors are the most common malignant tumors of the skeleton.

Approximately 70% of all malignant tumors are metastatic in origin.• metastases are usually found in: Vertebrae - especially posterior vertebral body,

extending into pedicle, pelvis, proximal femur, proximal humerus and skull.• Metastases distal to the elbow and knee are distinctly uncommon.

Types : - osteolytic metastases - sclerotic/osteoblastic metastases - mixed lytic and sclerotic metastases

Osteoblastic metastases Osteolytic metastases Mixed metastases

prostate carcinoma (most common) RCC Lung carcinoma (25%)

breast carcinoma (may be mixed) Thyroid carcinoma Breast carcimoma (15%)

transitional cell carcinoma (TCC) Pheochromocytoma carcinoma of cervix

carcinoid Wilms tumor testicular tumorsmedulloblastoma Ewings sarcoma Prostatic

carcinoma (15%)neuroblastoma Carcinomas of GITmucinous adenocarcinoma of GIT Melanomalymphoma HCC SCC of skin Uterine carcinoma

Metastases (contd.)Imaging Findings•  little or no soft tissue mass

associated with them• Usually no periosteal reaction• May appear as moth-eaten,

permeative or geographic lesions• Indistinct zones of transition, no

sclerotic margins and may be sharply circumscribed or have indistinct borders

• Lesions distal to elbows and knees - 50% are from lung and breast

• Diffuse skeletal sclerosis or multiple round, well-circumscribed sclerotic lesions - Prostate & Breast

• Expansile and lytic (soap-bubbly) - RCC

• Cookie-bite lesions of the cortices of long bones - Lung

• Bone scans are extremely sensitive but not very specific

• 10-40% of lesions will not be visible on plain film but will be positive on bone scans

• CT or MRI can be used to show findings in patients with negative conventional radiographs and positive bone scans

Metastases (contd.)

Fibrosarcoma• Fibrosarcoma is a tumor of

mesenchymal cell origin that is composed of malignant fibroblasts in a collagen background..

• It can occur as a soft-tissue mass or as a primary or secondary bone tumor.

• Primary fibrosarcoma - central (arising within the medullary canal) or peripheral (arising from the periosteum)

• Secondary fibrosarcoma of bone arises from a preexisting lesion or after radiotherapy to an area of bone or soft tissue.

• Fibrosarcomas of bone are typically seen between the third and sixth decades of life.

• most commonly in the metaphysis or metadiaphysis of the long tubular bones.

Fibrosarcoma (contd.)Plain Film  Highly destructive with a wide zone of

transition and often expansile. Periosteal reaction is uncommon.  The lesion usually has not matrix mineralization, but may have areas of sequested bone. Often associated with a large soft tissue mass.

CT     CT scanning is used to delineate bone

involvement, bone destruction, or bone reaction.

MRI best modality overall for examining soft-

tissue masses and for detecting the intraosseous and extraosseous extent of many bony sarcomas.

T1WI - IsointenseT2WI - HyperintenseShows strong enhancement on contrast

images

Pleomorphic undifferentiated sarcoma• Previously known as malignant fibrous

histiocytoma.• high grade tumor composed of

fibroblasts, myofibroblasts, and histiocytes.

•  most frequent soft tissue tumor in adults.

•  found in the extremities 70-75% of the time and 50% of all cases are in the lower extremity.

• highest incidence is during the fifth decade of life and there is a male to female ratio of 1.5 to 1

Plain Film Plain x-rays will demonstrate a soft

tissue mass and if arising from bone, then an aggressive destructive bony lesion. In some cases, curvilinear or punctate regions of calcification may be demonstrated.

Pleomorphic undifferentiated sarcomaCT• The density of MFH is typically similar

to adjacent muscle, with heterogeneous lower density areas if haemorrhage, necrosis or myxoid material is abundant.

• The soft tissue component enhances.• In up to 15-20% of cases some

mineralisation is present.

MRI     typically relatively well circumscribed,

located within or adjacent to muscle, exerting positive mass effect on surrounding structures.

T1WI - Highly variable, isointense (muscle), T2WI - intermediate to high signal intensityHeterogeneous and shows enhancement

of solid components.

Chordoma• Chordomas are uncommon malignant

tumours that account for 1% of intracranial tumours and 4% of all primary bone tumours.

• They originate from embryonic remnants of the primitive notochord.

• Occurs between the ages of 30-70 with a 2:1 male:female ratio

• 50% occur in sacrum, in  4th or 5th sacral segment.

• 35% at skull base around clivus• vertebral body: 15-30%

Plain Film• Large presacral mass (>10cm),

destruction of multiple sacral and coccygeal segments.

• Sclerotic rim in 50%,  amorphous calcifications ( mainly peripherally)

• May cross the sacroiliac joint•  Pattern is lytic, with sequestered bone

fragments.

Chordoma (contd.)CT• CT is helpful in defining bone destruction

and calcification within lesion.• With contrast, the pseudocapsule may

enhance. • Usually low attenuation soft tissue mass with

destruction of the sacrum and/or coccyx, sometimes with marginal sclerosis.

• May show sequestered bone fragments or calcifications within tumor.

MRIT1WI – intermediate to low signal intensity with

a small foci of hyperintensity (hemorrhage or mucus)

T2WI - most exhibit very high signal .T1 C+ (Gd): heterogeneous enhancement with

a honeycomb appearance corresponding to low T1 signal areas within the tumour

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PubMed;RSNA;KJR;IJR Metastatic diseases of bone – Learning Radiology