Lucent bone lesions (‘FEGNOMASHIC’). Infection and EG should be mentioned <30yo, metastases and infection >40yo.
- Fibrous dysplasia – No periosteal reaction.
- Enchondroma – Calcification (except phalanges), painless (no periostitis).
- Eosinophilic granuloma – <30yo.
- Giant cell tumour – Closed epiphyses, abuts articular surfaces in long bones, well defined with nonsclerotic margin in long bones, eccentric.
- Nonossifying fibroma – <30yo, painless (no periostitis), cortically based.
- Osteoblastoma (rare) – Similar to ABC esp posterior elements of spine.
- Metastases and Myeloma – >40yo.
- Aneurysmal bone cyst – Expansile, <30yo.
- Solitary bone cyst – Central, <30yo.
- Hyperparathyroidism (Brown tumour) – Must have other evidence of hyperparathyroidism.
- Infection – Always mention.
- Chondroblastoma (rare) – <30yo, epiphyseal.
- Chondromyxoid fibroma (rare) – Similar to NOF, no calcified matrix.
- Other rare lesions include intraosseaous ganglion, pseudotumour of haemophilia, haemangioendothelioma, ossifying fibroma, intraosseous lipoma, glomus tumour, neurofibroma, plasma cell granuloma, schwannoma.
Bony sequestrum – EG, osteomyelitis, lymphoma or fibrosarcoma; appearance of sequestrum with osteoid osteoma (nidus partially calcified).
- Epiphyseal and epiphyseal equivalents including apophyses, carpal bones (esp calcaneus), tarsal bones and patella – <30yo: infection, GCT, geode/subchondral cyst (OA, RA, CPPD, AVN), ganglion, chondroblastoma. >40yo add mets/myeloma and remove chondroblastoma; include unicameral bone cyst in calcaneus.
- Metaphyseal – Most lesions.
- Diaphyseal – Ewings, leukaemia, lymphoma, myeloma, adamantinoma, mets, fibrous dysplasia, UBC, Brown tumour.
- Central – UBC, enchondroma, FD, osteosarcoma, MFH, Ewings, leukaemia, lymphoma, myeloma, chondrosarcoma.
- Eccentric – ABC, GCT, enchondroma, CMF, osteosarcoma, MFH, Brown tumour.
- Intacortical – NOF, osteoid osteoma, LCH, Brodie abscess, osteofibrous dysplasia, adamantinoma, Brown tumour.
- Juxtacortical – Cortical desmoid, surface osteosarcoma, juxtacortical chondroma/chondrosarcoma, ABC, osteoid osteoma.
- Specific locations:
- Ribs (‘FAME’) – Fibrous dysplasia, ABC, Mets/Myeloma, Enchondroma (and other chondroid lesions) and EG.
- Sacrum – GCT, ABC, chordoma, neurogenic tumour, mets, myeloma, insufficiency fracture.
- Spine posterior elements – Osteoblastoma, ABC, mets, chondrosarcoma.
- Vertebral body – Haemangioma, GCT, LCH, mets, myeloma, Ewings, chondrosarcoma.
- Tibial cortex – Adamantinoma, fibrous dysplasia, haemangioma.
- Skull – Mets, myeloma, Pagets, haemangioma, epidermoid cyst, LCH.
Multiple lytic bone lesions ‘FEEMHI’ – Fibrous dysplasia, Enchondroma, EG, Mets/Myeloma, Hyperparathyriodism, Infection.
Lytic lesions with no pain/periostitis (unless trauma/fracture) – Fibrous dysplasia, enchondroma, NOF, solitary bone cyst.
Sclerotic bony lesions:
- Regression of lytic lesion filling with new bone (esp 20-40yo) – NOF, EG, ABC, solitary bone cyst, chondroblastoma, Brown tumour.
- Fibrous dysplasia
- Osteoid osteoma
- Giant bone island
- Metastases – >40yo.
Malignant bone tumours may be primary, secondary (underlying lesion) or metastatic. Descriminators include:
- Tumour margin and pattern of bone destruction – Most reliable, but only applies to lytic lesions, judged on the most aggressive margin. Wide if it is imperceptible, most likely aggressive (infection, EG, malignancy). Type 1 are geographic; 1A sclerotic rim (most nonaggressive), 1B narrow zone of transition (well-defined and able to be drawn with a pen or sclerotic margin), 1C broad zone of transition (most aggressive). Type 2 are moth-eaten, regional multi-focal with discrete holes. Type 3 are permeative from infiltration and enlargement of Haveresian systems, from small round cell tumours (multiple myeloma, lymphoma), Ewing sarcoma, infection, EG. Endosteal scalloping is sharply marginated destruction of inner cortex, may progress to cortical breathrough if aggressive or expansion if less aggressive.
- Tumour matrix – Lysis due to hormonal and mechanical factors (not direct destruction by tumour), at least 50% of trabecular bone lost before visible on XR. Calcification of osteoid may occur in early fracture healing, early myositis ossificans. Best seen on CT.
- Chondroid matrix – Enchondral ossification with circles/pieces of circles 1-2mm, ‘arcs and rings’, punctate, popcorn, ‘C- and J-shaped’ calcification, honeycomb, dense for it’s size.
- Osteoid matrix – Calcifies in amorphous, ivory, ‘cloud-like’, ‘fluffy’, ‘cotton-wool’ pattern; ground-glass typical in fibrous dysplasia.
- Nonmineralised matrix – Includes fluid, soft tissue or fat.
- Ossification – Well-defined trabeculae and cortex.
- Location – Flat or long bone; appendicular or axial; epiphyseal (chondroblastoma, geode, GCT), metaphyseal (osteosarcoma, chondrosarcoma, enchondroma, osteochondroma, GCT) or diaphyseal (round cell tumours: lymphoma, myeloma, Ewings); concentric, eccentric or surface.
- Periosteal reaction (periostitis, periosteal new bone formation) – Uninterrupted/solid/mature reaction in slow-growing/non-aggressive lesions causes thick, wavy, uniform or dense (time to lay thick bone and remodel into a more normal cortex). Interrupted in aggressive lesions, being lamellated/onion-skinned (separated by thin unossified matrix or tumour), amorphous or sunburst-like/spiculated/hair-on-end (highly aggresive), Codman’s triangle (triangular periosteal calcification at margin where periosteum not seen elsewhere due to destruction or elevated without time for new bone formation); but when irritation stops/diminishes this solidifies and appears benign. Aggressive periostitis is seen in infection, EG, ABC, osteoid osteomas, HPOA, trauma, healing fractures or malignancy. Nonagressive periostitis almost never malignancy (unless there is a concamitant fracture or infection).
- Cortical breakthrough/destruction – Suggests aggressive lesions including infection and EG. Tumours tend to displace adjacent fascial planes whereas infection obliterates. ABC can cause marked thinning of the cortex making it undetectable. Other benign lesions may have noncalcified matrices (fibrous or chondroid) that are lucent (cortical replacement rather than destruction).
- Age – Aggressive bone lesions and age:
- 1-30yo – Ewing sarcoma (permiative/moth-eaten, onion-skin periostitis, <10yo), osteosarcoma (sclerosis, 10-20yo), metastatic neuroblastoma (1yo), infection, EG.
- 30-40yo – Malignant giant cell tumour, parosteal sarcoma (sclerosis), fibrosarcoma (purely lytic), primary lymphoma of bone (permeative/moth-eaten).
- >40yo – Chondrosarcoma (amorphous snowflake calcification), metastases, myeloma.
- Orientation/axis of the lesion – Inaccurate. Benign lesions tend to be orientated along the long axis of a bone, malignant lesions tend to be circular.
Findings that don’t affect the differential diagnosis include soft tissue mass, bony expansion (except ABC), sclerotic/nonsclerotic border (except GCT), bony struts or compartments, size.
Work up for sarcomas includes XR (differentiate aggresive from benign) ± CT, MRI of whole bone (extent best on MR>CT>XR), bone scan and CT chest (metastases).
MRI is best for determining the extent of the lesion (skeletal and soft tissue), should be performed prior to any tumour resection. On MRI benign lesions tend to be well marginated, uniform and homogeneous signal, doesn’t encase neurovascular structures, doesn’t invade bone compared to malignant lesions; but these are relatively inaccurate. Almost all tumours have low T1 and high T2 (as are fluid collections, IM injection sites, trauma, oedema), except fibrosarcomas, desmoid tumours and calcification which may be both low T1 and low T2. T1WI show high tumour-to-fat/marrow contrast, T2WI high tumour-to-muscle contrast. The tumours that can be characterised better on MR are lipomas (high T1, sharp margins), haemangiomas/AVMs (mixed/low serpiginous flow voids), lobules of cartilage, fluid-fluid levels, highly ceullular lesions (relatively less signal eg lymphoma). Oedema surrounding tumours is indistinguishable from tumour spread, and areas of microinvasion may not be seen. Gadolinium should routinely be given (except obvious ganglion or bursa) to distinguish fluid (no or rim enhancement) from solid mass (diffuse enhancement).
- High T1 lesions – Fat (lipoma, liposarcoma, haemangioma, dystrophic fat), methaemoglobin/haemorrhage, Gadolinium enhancement, proteinaceous materal, melanin.
- Low T2 lesions – Hypocellular fibrous tissue (fibrous tumours, scar tissue), dense mineralisation, melanin, haemorrhage (acute or old haemosiderin), flow voids, gas, foreign body, gouty tophus, amyloidosis, methacrylate. Intermediate low in highly cellular tumours eg lymphoma.
- Fluid-fluid levels – ABC, telangiectatic osteosarcoma, GCT; less likely unicameral bone cyst, chondroblastoma, tumour necrosis, haematoma, haemangioma (if large low-flow channels present), cystic degeneration within fibrous dysplasia.
Permeative bone lesions (multiple small holes from endosteal involvement) – <30yo Ewing sarcoma, infection, EG; >30yo multiple myeloma, metastases, lymphoma. DDx pseudopermeative pattern (cortical holes) in aggressive osteoporosis, haemangioma, radiotherapy.
Fracture may mimic malignancy histologically (high nuclear-to-chromatin ratio, high mitotic figure count) and radiographically (extensive sclerosis, periostitis, exuberant callus with lack of immobilisation).
Periostitis in a long bone which is otherwise normal: HPOA, venous stasis, thyroid acropachy, pachydermoperiostosis, trauma.
Apart from osteomas, bone formation is usually immature woven bone and variable mineralised.
Round/oval sessile tumours projecting from subperiosteal surface, usually solitary, slow-growing, middle aged. Woven and lamellar bone, may have haversian-like systems, trabecula or marrow. Usually in membranous bones (calvaria esp external table, paranasal sinuses). May cause sinus obstruction or impinge on brain/eye/teeth. Densley sclerotic, well-defined margins, occasionally causes expansion. May be multifocal in Gardner’s syndrome.
(Bone island). Compact bone within medullary space, blending into trabeculae (with spicules, pathognomonic). May be large, always asymptomatic. Usually orientated in direction of trabeculae/stress (long bones ovoid parallel to long axis, spherical in metaphyses where trabeculae are more random). ?Hamartomas or failure of osteoclast activity during remodelling. >10mm unusual except for pelvis, >25mm are giant bone islands, may enlarge slowly. Usually negative on bone scan unless large (cf osteosarcoma).
Osteopoikilosis – Multiple bone islands clustered around joints, favouring appendicular skeleton.
Unknown aetiology, almost all <30yo, M:F 2:1, painful worse at night and releived by aspirin/NSAIDs (pain probably from excess prostaglanded E2 from osteoblasts). Variable appearance, classically cortically based sclerotic lesion in long bone with small <20mm lucency within (nidus, cause of pain and surrounding sclerosis, usually high T2, intense enhancement). Less sclerosis if nidus is medullary or in a joint. 80% intracortical. Common in femoral diaphysis, tibial diaphysis, femoral neck, posterior elements of spine (at concavity of scoliosis). Nidus may have calcification (DDx sequestrum, osteomyelitis), may be complete hence nidus invisible amongst sclerosis. Nidus extremely vascular with avid uptake on bone scan within reactive sclerosis (double-density sign) cf osteomyelitis (photopenic area from pus). Hypervascularity may cause growth deformity.
- Intra-articular/intracapsular lesions elicit little/no marginal sclerosis or periosteal new bone formation (no covering periosteum), but may have periostitis remote to the lesion (similar to chondroblastoma), may have chronic synovitis with effusion, cartilage loss, OA, lateral subluxation of femoral head.
- Subperiosteal lesions (esp talus) are round, soft tissue masses adjacent to bone causing scalloping, irregular bone resorption, litte reactive change.
- Periosteal (rare) cause exuberant periostitis.
DDx osteoblastoma (if nidus >20mm), chronic osteomyelitis (draining sinus with cloaca), stress fracture (improves with night and rest); intra-articular DDx infection, inflammatory arthritis, Perthes disease. Usually spontaneously regresses in ~3yrs. Tx surgical excision or thermal ablation of the nidus.
(Giant osteoid osteoma). Rare. Identical histology to osteoid osteoma, but >20mm, involves spine more frequently, pain is dull, unresponsive to aspirin, and doesn’t usually induce marked bony reaction. Expansile, may be lucent (most) mixed or blastic, ‘soap-bubble’ appearance (similar to ABC), narrow zone of transition with sclerotic border (type 1A). Common posterior elements of veretebrae (DDx ABC, TB), long bones. 50% have speckled calcification. DDx osteomyelitis, ABC (in spine), osteosarcoma. May rarely undergo malignant transformation if irradiated.
(Osteofibrous dysplasia). Extremely rare, benign, almost always anterior proximal tibia, young. Cortical oval lesion with expansion, bowing, sclerotic rim. May be lucent or have osteoid matrix. DDx cortical fibrous dysplasia (doesn’t have osteoblastic rim), adamantinoma.
(Osteogenic sarcoma). Most common malignant primary bone tumour. Almost all <30yo, but can be seen later as secondary osteosarcoma in Paget disease or radiotherapy. M:F 1.6:1. Anywhere in skeleton, more common toward end of long bone (metaphyseal), 50% about the knee. Usually destructive. Sclerosis from new bone formation or reactive, but occasionally entirely lytic. MR usually large soft tissue component with heterogeneous T1/T2. Commonly areas of haemorrhage and cystic degeneration. Tx amputation or radical excision.
- Central/conventional/intramedullary osteosarcoma (75%) – Most 10-25yo, 90% metaphyseal (may be diaphyseal), crosses into epiphysis in 75%. At sites of most rapid growth including distal femur, proximal tibia, proximal humerus, iliac wings. Rapid doubling rate, highly aggressive with permeative pattern, cortical breakthrough, often large soft tissue mass, aggressive periostitis (hair-on-end or Codman’s triangle). High T1 only if haemorrhage or Gadolinium. Osteoid matrix may be entirely lytic, amorphous/cloud-like calcification or densely blastic. On histology 50% osteoblastic (mostly osteoid), 25% chondroblastic (mostly cartilage), 25% fibroblastic (mostly spindle cells). Osteoid matrix in soft tissue mass is pathognomonic. DDx Ewing’s sarcoma (diaphysis or metadiaphyseal, may have extensive reactive bone formation mimicking osteoid matrix but doesn’t extend into soft tissue), healing fracture, early myositis ossificans, cortical desmoid. Metastases in 10-20% at presentation in same bone (skip lesion in 1-10%), lung. 80% of recurrences occur in lungs. Bone scan for ?polyototic involvement, chest CT, MRI for local extent (including whole bone). Restaged after chemotherapy prior to surgery, may develop further ossification due to cell maturation.
- Telangiectatic osteosarcoma (rare) – Similar age/distribution/prognosis/treatment as conventional osteosarcoma. Expansile, lytic, type 1C margins, cortical breakthrough. Highly vascular with necrotic tissue, large pools of blood (fluid-fluid levels), with tumour only at periphery and along septations (may be nodular/irregular). DDx ABC, GCT which don’t have nodules or broad zone of transition.
- Low-grade intraosseous osteosarcoma (rare) – Entirely intraosseous ranging from well-defined to permeative, diaphyseal or metadiaphyseal, entirely lytic to sclerotic. Slightly older median age. May not have as intense bone scan uptake as expected. Good prognosis if resected early.
- Surface osteoarcomas: parosteal > periosteal > high grade surface.
- Parosteal osteosarcoma (2nd most common) – From periosteum, growing outside bone, often wraping around diaphysis with lobulated margins, often large at presentation. Older age-group (20-50yo) than central osteosarcoma, M:F 2:3. Not as aggressive (low grade) and tends to be slow-growing, but once it violates the cortex (50%) it is as aggressive as central osteosarcoma (best seen on CT or MR). Lung metastases later and less frequent. Tend to be osteoblastic (cf periosteal). Densest calcification is central, faint calcification peripherally (reverse of myositis ossificans). Common posterior distal femoral metaphysis, proximal tibia, proximal humerus. DDx cortical desmoid tumour (benign, avulsion injury that may appear aggressive and malignant histologically), myositis ossificans (may appear malignant histologically). Tx en bloc excision.
- Periosteal osteosarcoma (rare) – Usually diaphyseal, esp femur and tibia, tends to be more medial at knee (cf parosteal posterior). 10s-20s, usually intermediate grade. Wraps around circumference of bone, may cause scalloping of cortex, occasionally cortical thickening. Periosteal rection with spicules of bone in sunburst pattern, Codman’s triangles. Emanating peripheral soft tissue mass. Rarely intramedullary extension. DDx juxtacortical chondroma. Prognosis better than central but worse than non-invaded parosteal.
- High-grade surface osteosarcoma (rare) – Diaphysis, similar appearance to periosteal osteosarcomas but much higher rate of intramedullary extension. Prognosis similar to central.
- Soft tissue osteosarcoma (rare) – 40-70yo, mostly thigh, occasionally upper limbs, retroperitoneum. Variable mineralised osteoid. Prognosis poor, worse than central osteosarcoma.
- Osteosarcomatosis (multicentric osteosarcoma) – Rare, often bilaterally symmetric, almost always osteoblastic, rapidly progressive. Most likely rapidly progressive metastases rather than true multicentric tumours with a dominant lesion and pulmonary metastases. Extremely poor prognosis.
Osteosarcomas in >60yo are more commonly axial skeleton (1/4) esp cranial/facial bones and soft tissues. 80% purely lytic. 1/2 primary; 1/2 secondary from Paget’s, previous radiation (DDx MFH, chondrosarcoma, undifferentiated sarcoma), dedifferentiated chondrosarcoma; rarely osteochondroma, osteoblastoma, bone infarct, fibrous dysplasia. Poor prognosis.
Predominantly hyaline or myxoid cartilage; fibrocartilage and elastic cartilage are rare components. Osteonecrosis may simulate chondroid matrix.
Benign tumours of hyaline cartialge, in any bone formed from cartilage, arising from residual rests displaced from growth plate. Within the medullary cavity (enchondromas) or surface of bone (subperiosteal/juxtacortical chondroma).
Enchondroma – Central or eccentric, expansile or nonexpansile. Usually monostotic, but may be multiple in hands/feet. Usually 20-40yo. Invariably calcified chondroid matrix except in phalanges. Often endosteal scalloping (cf bone infarct). Most common benign cystic lesion with thin lobulated sclerotic margins (C or O ring sign) in phalanges (50% in hands and feet), often presenting with fracture. Also commonly metaphysis of long bones (humerus, femur, tibia), rarely axial skeleton. Consider chondrosarcoma if pain, periostitis, endosteal scalloping >2/3 of cortical thickness, soft tissue mass, large or enlarging, destruction of previously present matrix or cortical breaththrough. DDx bone infarct (well-defined densely sclerotic serpiginous border); if no calcified matrix (hands and feet) GCT, epidermoid inclusion cyst, ABC, UBC, fibrous dysplasia. MRI lobules of intermediate T1 and very high T2 cartilage. Small risk of malignant transformation esp axial skeleton and proximal extremity; rare in hands or feet (regardless of radiographic appearance). Difficult/impossible to differentiate from chondrosarcoma radiographically or histologically hence biopsy should not be routine.
Multiple enchondromatosis (>1 other than hands and feet) are rare, not hereditory, appear in early childhood. Tend to be unilateral, localised to one extremity. May be typical enchondromas or large and grotesque (esp fingers), may be striated with vertical lucencies/densities. Might not have chondroid matrix. Limb usually short with epiphyseal deformity. Malignant transformation (usually chondrosarcoma) in 10-25%:
- Ollier disease
- Maffucci syndrome – Associated with soft tissue and visceral haemangiomas, phleboliths. Higher rate of malignant degeneration, ovarian carcinoma and brain gliomas.
Juxtacortical/subperiosteal chondroma – Benign, from periosteal surface with soft tissue mass, cortical pressure erosion, calcification in 50%, may have striking periosteal reaction. Wide age-range. DDx periosteal osteosarcoma (very similar appearances), GCT of tendon sheath with cortical saucerisation.
(Exostosis). Most common benign tumour, 3% of population, esp regions of rapid growth (distal femur, proximal humerus, tibia, fibula). 90% solitary, growth usually ceases at skeletal maturity. From displaced growth plate cartilage with lateral bone growth from metaphysis. Hyaline cartilage-capped bony outgrowth covered by perichondrium, may be pedunculated/cauliflower-shaped (usually extending away from joint) or sessile, must have continuity of normal marrow cortex periosteum and trabeculae. May contain chondroid matrix in the cartilaginous cap. Undertubulation (widened diameter of bone) almost always present at site of exostosis. Cx overlying bursitis, limited ROM, local compression. Malignant degeneration in cartilage cap rare (<1%), more common in axial lesions, pain (may have no other findings), destruction of previously present matrix, >15mm or irregular cartilage cap, growth of cartilage cap after skeletal maturity.
Multiple hereditary exostosis (diaphyseal aclasis) – Multiple osteochondromas (most sessile), autosomal dominant (mutations in EXT1 or EXT2 genes), short stature (diversion of physeal cartilage to osteochondromas), almost always involves knees. Smooth undulating cortex of long bone metaphysis and pelvis, coxa valga. Madelung deformity (epiphyseal arrest volar ulnar distal radius with correponding tilt) DDx dyschondroesteosis (type of dwarfism), Ollier’s disease, multiple epiphyseal dysplasia. Higher risk of malignant transformation (2-10% overall).
Trevor disease (dysplasia epiphysealis hemimelica, Trevor-Fairbank disease) – Multiple intra-articular epiphyseal osteochondromas in single/multiple joints, usually in only one extremity. Most commonly knee and ankle. Lobulatd mass from epiphysis.
(Codman’s tumour). Rare, usually benign, almost exclusively epiphyses/apophyses of skeletally immature teens, M:F 2:1, usually painful. Benign tumour composed of osteoblasts and scant amount of immature hyaline cartilage. Esp proximal femur, distal femur, proximal tibia, proximal humerus, hindfoot, pelvis, ribs. Typically sclerotic margins, lobulated, predominantly cystic but 50% calcified chondroid matrix (chicken-wire pattern). Most cause thick periosteal reaction along metaphysis remote from the lesion (?hormone mediated) with associated marrow and soft tissue oedema. May extend into metaphysis if physis is partially closed. May have joint effusion. Occasionally undergoes haemorrhagic cystic degeneration. Common recurrence after curettage. May have pulmonary metastases after fracture or repeated curettage, after being pushed into ruptured vessels. DDX GCT crossing into epiphysis, geode, clear cell chondrosarcoma, EG, osteomyelitis.
Very rare containing cartilage, fibrous and myxoid tissue. Teenages/young adults, M>F. Localised pain and swelling. Usually eccentric in metaphysis of long bones, but can involve any bone. 30-80mm. Thick sclerotic lobulated margins, may cause mild expansion. Rarely calcified matrix. Esp proximal tibia, proximal/distal femur, flat bones, tarsals, hands and feet. Similar to NOF, but any age. Often extend into epiphyses (cf NOF). Rarely progresses to aggressive/malignant lesion.
Protean appearance. Usually >40yo, M:F 2:1. Usually painful progressively enlarging, rarely involves distal extremities (cf enchondroma). Bony or soft tissue mass with amorphous snowflake calcification. Without calcified chondroid matrix it is indistinguishable from other aggressive lytic lesions (plasmacytoma, fibrosarcoma, infection). 90% are low-grade almost indistinguishable from enchondroma radiographically and histologically; it is also debatable whether these low grade tumours are even malignant. ‘Possible chondrosarcoma’ shoud be reserved for lesions that are painful or have definite aggressive features (periostitis, bony destruction), soft tissue mass or oedema on MR. Histologically are conventional (most, hyaline and/or myxoid), clear cell, dedifferentiated or mesenchymal variants. 15% arise from preexisting enchondroma/osteochondroma. Local recurrence more common than metastases. Prognosis worse for proximal and axial lesions. Dedifferentiated chondrosarcoma – portion of low-grade chondrosarcoma dedifferentiated into a high-grade lesion (in ~10%) which may contain elements of fibrosarcoma, osteosarcoma (usually chondroblastic osteosarcoma); poor prognosis, lung metastases common. Pure high grade chondrosarcomas are uncommon.
- Conventional chondrosarcoma – Hyaline and/or myxoid elements.
- Central/intramedullary chondrosarcoma (90%) – Primary (usually proximal) or secondary (eg enchondroma). Common, undiagnosed (may appear benign). Central, metaphyseal, esp proximal long bones, pelvis, shoulder. 30s-50s. 90% low grade, generally large (>50mm), may have narrow zone of transition with non-sclerotic border, endosteal scalloping (>2/3 cortical thickness cf enchondroma). Range from completely lytic (more commonly low-grade due to more myxoid tissue) to dense chondroid matrix. High-grade lesions may have cortical breakthrough, soft tissue mass. Variable periosteal reaction, endosteum may be thickened (DDx primary lymphoma, Ewing’s, osteomyelitis).
- Peripheral/exostotic/juxtacortical/surface chondrosarcoma – Primary or secondary (eg osteochondroma), 20s-40s. Large extraosseous from metaphysis, esp pelvis, shoulder, sternum, ribs. May have normal appearing host bone extending into exostosis. Higher-grade lesions have destruction of stalk, soft tissue mass beyond cartilaginous cap.
- Clear cell chondrosarcoma (very rare) – Younger <30yo, almost identical appearance to chondroblastoma being epiphyseal (esp proximal femur and humerus), sclerotic margin. Periosteal reaction and cortical breakthrough rare. Chondroid matrix usually absent.
- Mesenchymal chondrosarcoma (very rare) – High-grade chondrosarcoma, young (<30), from soft tissues, rib, jaw. Aggressive with chondroid matrix.
Benign hamartomatous metaplasia/dysplasia, fibrous stroma with islands of osteoid and woven bone. Congenital but presenting at any age, may look like almost any other pathologic process. Wild-looking, patchy, expansile (relatively long length of invovlement cf degree of expansion), cortical thinning, multiple, ground-glass/smoky matrix (lytic with calcified matrix). Bone is soft with deformities including bowing, angulation, shepherd’s crook (varus femoral neck). In long bones usually central and metadiaphyseal. Usually purely lytic, ongoing calcification of the matrix -> sclerotic lesion. No periostitis. Virtually never malignant degeneration. Usually painless unless fracture (may be occult, unusual in non-weightbearing flat bones/ribs). Monostotic (most common) or polyostotic (30%, usually <10yo, usually hemimelic only one limb). In any bone (uncommon in spine) esp pelvis (always also involves ipsilatearl proximal femur, typically expansile and bubbly), proximal femur (sparing of pelvis is common), ribs (expansile lytic posterior ribs; sclerotic anterior ribs), skull (esp base more sclerotic, calvarium expansive lytic/dense). Increased bone scan uptake. MRI isointense to muscle, frequent uniform enhancement. Occasional cystic degeneration with fluid-fluid levels. DDx Paget’s disease, NF1. Most remain quiescent, 5% enlarge after skeletal maturity. Rarely malignant transformation (fibrosarcoma, osteosarcoma).
- Cherubism – Rare congenital multiple lesions in jaw causing puffed out cheeks, angelic look, abnormal dentition. Tends to regress in adulthood.
- Leontiasis ossea – Craniofacial involvement in polyostotic form, esp sphenoid bones, frontal, maxillaary and ethmoid. Bony expansion causes deformity, cranial nerve compression, exophthalmos.
- McCune-Albright syndrome – Polyostotic form with cafe-au-lait spots (dark freckel-like skin lesions) with irregular ‘coast of Maine’ margins (cf NF1 smooth ‘coast of California’) and endocrine disorder (usually precocious puberty or hyperthyroidism).
- Mazabraud syndrome (rare) – Associated with intramuscular myxomas (benign mass predominantly myxoid tissue of very high T2 and peripheral/septal enhancement), usually near abnormal bones.
Metaphyseal Cortical Defect
(Fibroxanthoma). 20% of children, usually spontaneously regresses hence rare >30yo. Termed fibrous cortical defect (FCD) if <20-30mm, nonossifying fibroma (NOF) if >20-30mm bubbly; both histologically identical. Not a true neoplasm, but from a physeal defect (?trauma at muscle attachment causing fibrous proliferation) migrating from physis with growth, must be asymptomatic. 80% in diametaphysis of lower limb long bones, esp around knee, occasionally multiple. Cortically based, may extend into intramedullary region and appear central, doesn’t extend into epiphysis. Usually have thin scalloped sclerotic border thicker on medullary margin, slightly expansile. No periostitis (except fracture), no matrix calcification. May become large with more bubbly appearance. May cause fracture esp if >50% of bone diameter (but prophylactic curretage usually not suggested). On CT/MR often appears to have interrupted cortex representing replacement by benign fibrous tissue. Involutes spontaneously, disappearing/healing NOF has homogeneous sclerosis by ~20-30yo, ‘melting’ into the normal bone, can be hot on bone scan. Multiple NOFs associated with NF1, Jaffe-Campanacci syndrome (multiple NOFs with cafe-au-lait spots without NF; associated with mental retardation, precocious puberty, hypogonadism, cadiovascular and ocular abnormal).
Benign Fibrous Histiocytoma
Rare, similar histology to NOF. Geographic, central, metaphysis of long bones. May be symptomatic, may originate in soft tissue. Tend to recur after curettage.
Liposclerosing Myxofibrous Tumour (LSMFT)
(Polymorphic fibro-osseous lesion of bone). 30s-50s. >90% central metadiaphysis of proximal femur. Usually lytic/ground-glass, markedly sclerotic border, amorphous globular/irregular matrix. Heterogeneous T2, more homogeneous T1 isointense to muscle. Complex immature bone and fibrous tissue, fat, xanthomatous and myxoid elements, may have ischaemic ossification. Small risk of malignant transformation requiring follow-up.
Marrow Tumours and Metastases
Primarily children and adolescents, almost all <30yo, peak 10-20yo; most common bone malignancy <10yo, second to osteosarcoma <20yo. Rare in blacks. Typically systemically symptomatic with fever, raised WCC and ESR. Translocation chromosome 11;22, histology and radiology similar to other small round cell tumours (lymphoma, leukaemia, PNET, metastatic neuroblastoma). Classically permeative with large soft tissue mass in central diaphysis or metadiaphysis of long bone in a child. Tends to involve long bones <10yo; pelvis, vertebrae, ribs or shoulder girdle >10yo. May be permeative and completely lytic (most), partially sclerotic (reactive new bone, may be thick reactive endosteal bone formation) or patchy; no new bone formation within soft tissue component. Prominent periostitis often onion-skin, but can be sunburst-like or amorphous; rarely benign. Initially monostotic, metastases to bone and lung common. DDx other small round cell lesions (neuroblastoma mets, lymphoma, PNET, leukaemia), infection and EG; can be radiographically and clinically identical.
Most common primary bone tumour, usually >35yo, may precede clinical/haematologic evidence by 3-5yrs. Proliferation of plasma cells originating in red marrow progressing to cortex. Esp skull, vertebral bodies, ribs, pelvis, proximal appendicular skeleton. May be solitary (plasmacytoma), but most multiple. Numerous focal punched-out lytic lesions with narrow zone of transition, usually <50mm. May be diffusely permeative (DDx Ewing, lymphoma). Occasionally presents as generalised osteopenia without focal lesion. Frequently involves calvaria with multiple small well-defined lucencies. Rarely sclerotic myeloma (associated with POEMS syndrome = polyneuropathy, organomegaly, endocrinopathy, myeloma, skin changes) as sclerotic marin or entirely sclerotic round lesions. Only lesion that isn’t hot on bone scan (only shows if microfractures) but scan does show ~20% of lesions not seen on XR skeletal survey; radiologic skeletal survey shows ~40% of lesions not seen on bone scan. Whole body MRI most sensitive generally mottled/diffuse/numerous low T1 and high T2. DDx metastases, multiple brown tumours of HPT. 10-15% associated with amyloidosis which may deposit in synovium mimicing RA. Poor prognosis. Lesions >50% of cortical width are at risk for pathologic fracture.
Plasmacytoma – Occasional presentation of myeloma being solitary, bubbly, lytic geographic without sclerotic margin, expansile, no matrix calcification. Can mimic any benign or aggressive lytic lesion. Common in areas of red/haematopoietic marrow including vertebral bodies, pelvis, femur, humerus. Most progress to multifocal/generalised disease within a few years.
Primary Lymphoma of Bone
(Previously reticulum cell sarcoma). Uncommon, most 30-60yo, usually DLBCL or follicular. Permeative or moth-eaten bony destruction, usually lytic but maymay have some sclerosis and endosteal thickening due to reactive bone formation similar to Ewing sarcoma. Occasionally ivory vertebra. Usually central diaphyseal/metadiaphyseal appendicular skeleton (esp femur, tibia, humerus); occasionally pelvis, scapula, spine. Only malignant tumour that can involve a large amount of bone while asymptomatic (cf Ewing). May enlarge rapidly with very large soft tissue mass without extensive cortical destruction (spreads through Haversian channels), may have bony sequestra. Uptake of bone scan, often before radiographic findings. Metastases to LN and bone; lung metastases uncommon.
In Hodgkin’s disease 20% have bone involvement by haematogenous or direct spread from adjacent nodes (esp sternum). Peak 30s. Most axial skeleton esp vertebrae. Most blastic or mixed, may be lytic. Ivory vertebrae (also seen in metastases and Paget’s) – increased density while retaining size and contours. 2/3 polyostotic.
Metastatic non-Hodgkins lymphoma indicates aggressive tumour with poor prognosis.
Usually >40yo. 80% from lung, breast, prostate, kidney; others include GIT, thyroid, round cell malignancies. Variable appearances. Most appear aggressive moth-eaten or wide zone of transition, but may look benign. Usually little periosteal reaction or soft tissue mass. Most central, in areas of red marrow (axial skeleton, proximal humerus/femur); lesions distal to elbows/knees usually from lung cancer. Occasionally cortically based esp lung, breast. Almost any bone metastasis can be lytic or blastic (except RCC). Purely lytic metastases usually lung, kidney, breast, thyroid, GIT, neuroblastoma. Bubbly lytic expansile metastases tend to be thyroid or renal (almost always lytic), also tend to be highly vascular at risk of bleeding. Blastic metastases include prostate or breast; less commonly lung, GIT (adenocarcinoma and carcinoid), lung (usually small cell), medulloblastoma, secondary lymphoma. Mixed lytic and blastic metastases include breast, lung, prostate, bladder, neuroblastoma. Change in density occurs with therapy or radiation necrosis. Lesions >25mm or >50% cortical width destruction are at risk of fracture. Lesser trochanter avulsion fractures in adults should be considered pathologic until proven otherwise, esp lung, myeloma, RCC. Solitary sternal lesion in breast cancer are rare, but 80% chance of being a metastasis. Transvere fracture in long bones are highly likely to be pathologic.
Miscellaneous and Tumour-Like Lesions
Giant Cell Tumour (GCT)
Common, multinucleated osteoclastic giant cells and fibrous stroma, with the tumour cell being the spindle cell in the stroma. 5% are malignant (30-40yo), unable to determine radiographically or histologically. Assumed to be malignant if recurs (can still be benign, tends to be more aggressive) with new/enlarging/asymmetric lytic regions in tumour bed, rarely metastasize (lung, even if benign = benign metastasizing GCT). Tend to be large at presentation. Almost all occur after physeal closure, most 20s-40s, F>M. Most at knee, distal radius/ulna, proximal humerus, spine (sacrum or vertebral body). Usually solitary, some multiple esp skull and facial bones in Paget’s disease. Usually eccentric in metaphysis extending into epiphysis to articular margin, narrow zone of transition, no marginal sclerosis, often mildly expansile. Occasional appears aggressive with cortical breakthrough and soft tissue mass. No calcified matrix. Typically uniform intermediate/low T1, nodular/zonal/whorled/uniform low T2 (high cellularity, haemosiderin, collagen deposition), occasionally fluid-fluid levels. DDx ABC (may also coexist), subchondral cyst or Brodie’s abscess (no expansion), chondroblastoma, Brown tumour.
Giant cell reparative granuloma – Non-neoplastic reactive lytic lesion in jaw, maxilla, hands, feet. Radiographically similar to GCT and contains giant cells at histology, but otherwise unrelated to GCT.
Aneurysmal Bone Cyst (ABC)
Benign, blood-filled cystic cavities ?vascular anomaly interfering with venous drainage. Typically <30yo, presents with pain. Monostotic in metaphysis/metadiaphysis, common in in posterior elements of spine, occasionally pelvis. Almost always eccentric, aneurysmal/expansile (rarely presenting before this), narrow zone of transition with fine uninterrupted sclerotic rim/cortex (may not be seen on XR). Usually has fluid-fluid level. Secondary type (30-50%) in conjunction with another lesion (GCT, chondroblastoma, fibrous dysplasia, osteoblastoma, NOF) or ?from trauma; suggested by thick rind/septations or peripheral nodule/mass. Primary type has no known cause/association (?ABC obliterating the precursor lesion, ie ?all actually secondary). Tx curettage with recurrence 20-50%, need to consider/check for underlying lesion.
Unicameral Bone Cyst (UBC)
(Solitary/simple bone cyst SBC). Common, usually asymptomatic unless fractured (common), almost always <30yo. Always centric. 2/3 in proximal humerus and proximal femur; in adults also iliac wing, calcaneus, talus. Arises from the physis and ‘grows’ into the shaft, but may grow into epiphysis after physeal closure. Most geographic with sclerotic margins, occasionally nonsclerotic margins. Single communicating space, may have some internal septations. May be mildly expansile. No calcified matrix. Common in calcaneus adjacent to inferior surface (not at risk of pathological fracture); DDx pseudocyst of the calcaneus (relative lucency at anteroinferior calcaneus from reduced stress in this region), intraosseous lipoma. No periostitis. Fallen fragment sign (pathognomonic) – piece of cortex fractures, sinking to dependent portion of lesion indicating fluid-filled cystic lesion. May mimic fibrous displasia after fracture. High T2, low T1, fluid-fluid levels if previous trauma (haemorrhage), very fine rim of enhancement. Often prophylactically curettaged and packed to prevent fracture and deformity (except calcaneus). Tx curettage or steroid injuections, high recurrence rate.
Protean appearance, any location and age. Will be in almost any differential of lytic bone lesion. May have obliteration of soft tissue fat planes. If abuts the articular surface, joint is invariable involved with cartilage loss and/or effusion. May be expansile, may have sclerotic or nonsclerotic border. May have periostitis. May have bony sequestrum, involucrum. CT recommended to check for sequestrum (requires surgery). Brodie abscess – subacute osteomyelitis which may persist for years.
Low-grade malignancy from notochord remants, most 30s-60s, M>F. 50% from sacrum and cocyx (40% of sacrococcygeal tumours), 35% clivus and 15% spine (esp lumbar and C2, beginning midline in vertebral body). Extensive local bone destruction, large soft tissue mass extending into spinal canal or paraspinal tissues infiltrating other soft tissues. Usually slow-growing with narrow zone of transition, sclerotic margins. Occasional haemorrhage and cystic change. Frequent amorphous calcification. Clival chordoma is more central than chondrosarcoma (which tends to arise more laterally at petroclival suture), elevated ADC values (cf chondrosarcoma low ADC). Chondroid variant in skull base is similar to low-grade chondrosarcoma on imaging. Metastases uncommon (lung), but poor morbidity due to local neurological involvement, frequent local recurrence with seeding. DDx chondrosarcoma (can be off midline), metastases, myeloma, GCT, lymphoma.
Rare malignant tumour with squamous, alveolar and vascular tissues. Almost exclusively in mid/proximal anterior tibial diaphysis (80-90%). Usually eccentric/cortical. Early geographic bone destruction, later aggressive, bubbly lytic, often sclerotic margins. May have satellite foci in tibia or fibula. Locally nonaggressive and may be present for years before metastases (20%) to lung, LN, bones; local recurrence common. DDx fibrous dysplasia, ossifying fibroma; ?spectrum of all 3 diseases, similar histology except adamantinoma has epithelial tumour cells.
Ameloblastoma (previously termed adamantinoma of the mandible) is unrelated to adamantinoma.
Accumulation of osteoclasts with expanded lytic lesions in hyperparathyroidism, generally undergoing sclerosis and disappears with treatment. More common in primary HPT, but more commonly seen in secondary due to higher prevalence of secondary HPT. Other features of HPT must be seen eg subperiosteal bone resorption (pathognomonic, esp radial aspect middle phalanges as indistinct interrupted cortex, distal clavicle resorption, medial aspect proximal tibias, SI joints), physes (if open) have frayed ragged appearance. Renal osteodystrophy wih secondary HPT may show osteoporosis/osteosclerosis.
Early infarct can be patchy or mixed lytic/sclerotic, may resemble a permeative process. May be multiple, in diametaphyseal region of long bones. Increased risk with sickle cell anaemia, SLE. Lytic lesion with calcified serpiginous borders (characteristic, best seen on MR).
Langerhans Cell Histiocytosis (LCH)
(Formerly histiocytosis X). Rare group of diseases with infiltrating langerhans cell, eosinophils, neutrophils and macrophages. ?Reactive or neoplastic. Predominantely children, M>F.
- Eosinophilic Granuloma (EG) – Most common, benign, almost always <30yo (most 5-15yo). Usually painful. Usually solitary (skull in 50%, spine, jaw, long bones esp femur), can be polyostotic (in 10-20%, esp younger patients). Variable apperances. Usually central metadiaphyseal (may be any part of bone), starts as highly aggressive moth-eaten/permeative, aggressive periosteal reaction (lamellated/amorphous); later healing (months to years) becoming well-defined ± sclerotic border, solid periosteal reaction (thick uniform wavy). May have mixed agressive/non-aggressive appearances (classic). May have soft tissue mass. Occasional bony sequestrum (also seen in osteomyelitis, lymphoma, fibrosarcoma). Skull lesions have narrow zone of transition, uneven inner/outer table involvement giving beveled-edge appearance or concentric lytic discs, don’t tend to have sclerotic margin. Vertebral bodies classically vertebra plana (DDx fracture, tumour, infection, AVN) with intact posterior elements and disk, lacks soft tissue mass. DDx Ewing’s sarcoma, lymphoma, osteomyelitis, aggressive metastases.
- Hand-Schuller-Christian disease (20%) – Chronic multiorgan, 2-10yo with proptosis, diabetes insipidus, lytic bone lesions. Occasional thymus, liver and lung involvement, spontaneous pneumothoraces, pulmonary fibrosis. Low mortality unless lungs involved.
- Letterer-Siwe disease (10%) – Most severe form with aggressive multisystem disease in <2yo, M>F. Small lytic lesions (esp skull) in 1/2, hepatosplenomegaly, lymphadenopathy, pancytopaenia (infiltration of marrow space), skin infiltration. Mortality >50%.
Erdheim-Chester disease – Rare non-Langerhans histiocytosis in adults with painful sclerosis of long bones, spares epiphyses. Multi-organ infiltration with macrophages, multinucleated giant cells, lymphocytes, histiocytes. Poor prognosis causing organ failure.
Rare, unknown aetiology. Severe pain, overlying skin thickening/fibrosis, muscle atrophy. Thickened cortical new bone near ends of long bones, usually only on one side of the bone like ‘dripping candle wax’. Follows a sclerotomal distribution. May cross joint with joint fusion. May be associated with osteopoikilosis, osteopathia strata, tumours of vascular malformations.
(Voorhoeve disease). Multiple 2-3mm thick linear bands of sclerosis parallel to long axis of a bone, usually multiple bones. Asymptomatic.
Hereditary, asymptomatic. Multiple small 3-10mm sclerotic lesions esp juxta-articular long bones and pelvis.
Rare, hereditary, more common in blacks. Skin thickening in extremities and face, finger clubbing, widespread periostitis. Only occasionally painful.
Bones involved in 10% esp middle or distal phalanges of hands, less frequently spine and long bones. Lacelike bony destruction in multiple phalanges of one/both hands (characteristic). Generalised osteopenia, scleorsis of phalangeal tufts, focal/generalised sclerosis. MRI shows bone marrow granulomas with high T2, intermediate T1, enhancement (DDx mets). Chronic sarcoidosis -> granulomatous arhtritis with synovial thickening and enhancement. Muscular sarcoidosis with enhancing nodules, low signal spiculated centres, generalised sarcoid myositis with proximal muscle atrophy.
Staging and Treatment
Enneking staging applies to primary bone tumours and soft tissue sarcomas. If a tumour enters a compartment, the entire compartment is considered contaminated. Stage Ia is G1T1M0; Ib G1T2M0; IIa G2T1M0; IIb G2T2M0; III G*T*M1.
- Grade (histologic) at biopsy – G0 benign; G1 low grade malignant; G2 high grade malignant.
- Site (radiographic and clinical) usually determined at MRI.
- T0 – Limited by capsule of reactive tissue.
- T1 – Extracapsular, intracompartmental. Compartments classified as: a skin/subcutaneous, b paraosseous (pushes muscles away from bone without invasion of cortex or muscle), c bone/intracortical (or single ray of hand/foot), d muscle compartment (limited by fascial planes).
- T2 – Extracapsular, extracompartmental or abuts major neurovascular structures.
- Metastases, usually bone or lung – M0 no metastases, M1 metastases.
Bone lesion workup – If it appears non-aggressive on XR then no further workup required. If appears aggressive, then bone scan (?polyostotic), chest CT (?mets), MRI and biopsy. Soft tissue lesion workup includes XR then MRI then biopsy then chest CT if malignant. Biopsy needs to be representative in regions of most aggressive features or oedema, away from necrotic areas. Needle approach needs discussion with oncological surgeon taking into consideration seeding, avoiding more than one compartment, suprapatellar bursa (is larger than expected) and gluteal muscles (if needed for coverage of resection).
- Intralesional excision (curettage) – Incomplete resection with tumour cells left at margins.
- Marginal excision (excisional biopsy) – Satellites of residual tumour may be left behind.
- Wide excision – Entire lesion removed surrounded by intact cuff of normal tissue, well beyond reactive tissue on imaging.
- Radical resection – Lesion removed with entire muscle, bone and other tissues within the compartment
80% of sarcomas that reccur do so within 2yrs. Suggested followup MRI (or CT ± US) at 3/12 then 6-monthly for 5yrs, then yearly for 5 yrs. DDx of postop high T2 includes seroma, haematoma, radiation change, fat necrosis, packing material, scar tissue, herniation of other tissue. Enhancing nodules or dynamic MRI increases specificity.
Best imaging indicator for response to chemotherapy is percentage of tumour necrosis, >50% reduction in product of 2 largest diameters (except osteosarcoma may show little change), rate of contrast enhancement on dynamic MRI (malignant tumours enhance more rapidly), PET. Non-irradiated bones may reconvert to haematopoietic marrow esp with chemotherapy, causing low T1. Lesions treated only with chemotherapy may heal with bizarre appeances similar to Pagets.
Complications of radiation therapy include:
- Tumour recurrence
- Early growth cessation – Physeal widening, metaphyseal fraying prior to fusion.
- Growth deformities
- Radiation-induced osteochondroma
- Radiation osteonecrosis – Mixed lysis and sclerosis, often aggressive, may cause fracture, susceptible to infection.
- Radiation-induced sarcoma – High grade osteosarcoma, fibrosarcoma, chondrosarcoma; developing after 4-20yrs.