Bone Tumors
Bone tumours feel like the part of orthopaedics that must simply be memorised, because there are dozens of lesions with unfamiliar names and overlapping appearances.
They are not. Radiologists and orthopaedic oncologists reach a diagnosis by asking three questions in a fixed order, and the order does most of the work. A candidate who asks the same three questions will out-perform one who has memorised twice as many lesion names.
1. Three Questions
| Question | What it tells you |
|---|---|
| How old is the patient? | Narrows the list to two or three possibilities |
| Where in the bone is the lesion? | Narrows it further, often to one |
| What is the bone doing about it? | Tells you whether it is slow and benign or fast and malignant |
The third question is the one candidates skip, and it is the most powerful. A radiograph does not show a tumour directly. It shows the bone's reaction to the tumour, and the vigour of that reaction reflects how much time the bone has had.
2. Reading Aggression
A slow lesion gives the bone time to wall it off. A fast lesion does not.
The zone of transition is the single most useful sign. A narrow zone, where you can draw the edge of the lesion with a pencil, means slow growth. A wide zone, where the lesion fades imperceptibly into normal bone, means the tumour is outrunning the bone's ability to respond.
| Pattern | Meaning |
|---|---|
| Geographic, sharply marginated, sclerotic rim | Slow, almost always benign |
| Moth-eaten | Intermediate aggression |
| Permeative, multiple tiny holes | Fast, malignant, classically Ewing sarcoma |
Periosteal reaction follows the same logic, since the periosteum lifts and lays down new bone at whatever rate it can manage.
A solid, thick, uninterrupted periosteal reaction means slow, because the periosteum kept pace. A lamellated or onion-skin reaction means repeated bursts of growth. A sunburst or spiculated reaction and a Codman triangle mean the periosteum was lifted faster than it could ossify, and the triangle is simply the ossified edge where it remained attached.
Matrix mineralisation names the tissue. Cloud-like or fluffy density means osteoid and therefore a bone-forming tumour. Rings and arcs, or popcorn calcification, mean chondroid and therefore a cartilage tumour.
3. Age as the First Filter
| Age | Consider first |
|---|---|
| Under 5 | Metastatic neuroblastoma, Langerhans cell histiocytosis, leukaemia |
| 5 to 25 | Ewing sarcoma, osteosarcoma, simple bone cyst, osteoid osteoma |
| 20 to 40 | Giant cell tumour |
| Over 40 | Metastasis, myeloma, chondrosarcoma |
In a patient over 40, a destructive bone lesion is a metastasis or myeloma until proved otherwise, because secondary deposits are far commoner than primary bone malignancy at every adult age.
Giant cell tumour occupies a narrow window, because it requires a closed physis and becomes uncommon later, which is why it is so tightly linked to the twenties and thirties.
4. Site Within the Bone
| Location | Suggests |
|---|---|
| Epiphysis | Giant cell tumour after physeal closure, chondroblastoma before it |
| Metaphysis | Osteosarcoma, simple bone cyst, aneurysmal bone cyst, osteochondroma, non-ossifying fibroma |
| Diaphysis | Ewing sarcoma, fibrous dysplasia, adamantinoma, lymphoma |
The epiphyseal pair is the highest-yield site rule in the chapter. A lucent epiphyseal lesion in a skeletally immature patient is a chondroblastoma; the same location after physeal closure is a giant cell tumour.
Position across the bone matters too. Eccentric lesions sit to one side of the medullary canal, which is characteristic of giant cell tumour, aneurysmal bone cyst and non-ossifying fibroma, whereas simple bone cysts are central.
5. Osteosarcoma
Osteosarcoma is the commonest primary malignant bone tumour, peaks in the second decade, and arises in the metaphysis of a rapidly growing bone, most often around the knee at the distal femur or proximal tibia.
The radiograph shows an aggressive metaphyseal lesion with a wide zone of transition, cloud-like osteoid matrix, a sunburst periosteal reaction and a Codman triangle. Alkaline phosphatase is often raised and correlates with tumour bulk.
Metastasis is haematogenous and goes to the lung, which is why staging always includes chest imaging and why pulmonary metastasectomy has a genuine role.
Treatment is neoadjuvant chemotherapy, then surgery, then further chemotherapy. The standard regimen is methotrexate, doxorubicin and cisplatin, together called MAP.
Neoadjuvant chemotherapy achieves three things: it treats micrometastatic disease immediately, it shrinks the tumour to make limb salvage feasible, and it allows the resected specimen to be assessed for percentage necrosis, which is the strongest available prognostic marker. Necrosis of ninety percent or more indicates a good response.
Five-year survival in localised disease is around 65 to 70 percent, and limb salvage surgery gives survival at least as good as amputation. That figure has changed little in four decades, which is an honest reflection of a therapeutic plateau since MAP was established.
A secondary osteosarcoma arises in Paget disease or in previously irradiated bone, occurs in older patients, and carries a worse prognosis.
6. Ewing Sarcoma
Ewing sarcoma is the great mimic of osteomyelitis, and the resemblance is close enough to be dangerous.
It occurs in children and young adults, affects the diaphysis of long bones and the flat bones of the pelvis, and presents with pain, swelling, fever, raised inflammatory markers and leucocytosis, all of which point towards infection.
The radiograph shows a permeative destructive lesion with a lamellated onion-skin periosteal reaction and a large soft tissue mass, which is often disproportionate to the bone destruction.
Histology is a small round blue cell tumour with membrane positivity for CD99, and the defining lesion is the translocation between chromosomes 11 and 22 producing the EWSR1-FLI1 fusion.
Ewing sarcoma is radiosensitive, which osteosarcoma is not. Treatment is chemotherapy followed by local control, and local control may be surgery, radiotherapy or both, which is a genuine difference from osteosarcoma where radiotherapy has little role.
7. Chondrosarcoma
Chondrosarcoma is a disease of older adults, arising in the pelvis, proximal femur and shoulder girdle rather than around the knee.
The radiograph shows rings-and-arcs chondroid calcification with endosteal scalloping, meaning erosion of the inner cortex, and cortical thickening.
Distinguishing a low-grade chondrosarcoma from an enchondroma is genuinely difficult, and the features favouring malignancy are pain in the absence of fracture, a lesion larger than five centimetres, endosteal scalloping over more than two-thirds of the cortex, and cortical destruction.
Chondrosarcoma is both chemoresistant and radioresistant, so surgical excision with adequate margins is the entire treatment, and that fact alone determines the answer to most management questions about it.
8. Giant Cell Tumour
Giant cell tumour arises in the epiphysis after physeal closure and extends to the subchondral bone, typically around the knee or at the distal radius.
The radiograph shows an eccentric, expansile, purely lytic lesion with a narrow zone of transition and no matrix mineralisation, often described as soap-bubble.
The 2020 WHO classification defines it as an intermediate, locally aggressive tumour rather than benign, reflecting a high local recurrence rate and the capacity for pulmonary metastasis in a small minority, which are histologically benign deposits.
The H3F3A mutation is a specific molecular marker and has become useful diagnostically.
The neoplastic cell is the mononuclear stromal cell, not the giant cell. It expresses RANK ligand, which recruits and activates the osteoclast-like giant cells that do the bone destruction.
Denosumab, a monoclonal antibody against RANK ligand, exploits that mechanism directly, and it has a specific and nuanced role.
Given before en bloc resection of a pelvic or spinal tumour it hardens the lesion and facilitates surgery. Given before curettage it should be avoided, because the peripheral rim of new bone it induces obscures the tumour interface and is associated with increased local recurrence.
Standard treatment for an appendicular lesion is extended curettage with an adjuvant such as phenol, liquid nitrogen or a high-speed burr, and cement filling.
9. Benign Lesions Worth Recognising
Osteoid osteoma causes night pain dramatically relieved by non-steroidal anti-inflammatory drugs, which is close to diagnostic. The nidus is a small lucency under 1.5 centimetres surrounded by dense reactive sclerosis, and the pain is prostaglandin-mediated, which is exactly why the drugs work. Radiofrequency ablation is standard treatment.
Osteoblastoma is histologically similar but larger than two centimetres, more often in the spine, and lacks the striking response to anti-inflammatory drugs.
Osteochondroma is the commonest benign bone tumour. It is a metaphyseal bony outgrowth capped with cartilage, and its cortex and medulla are continuous with those of the host bone, which is the definitive radiological feature. It points away from the adjacent joint.
Malignant transformation is suggested by growth after skeletal maturity, new pain, or a cartilage cap thicker than two centimetres, and the risk is higher in hereditary multiple exostoses than in a solitary lesion.
Simple bone cyst is central, in the proximal humerus or femur of a child, and presents with pathological fracture; the fallen fragment sign is characteristic.
Aneurysmal bone cyst is eccentric, expansile and blood-filled, and shows fluid-fluid levels on magnetic resonance imaging.
Non-ossifying fibroma is an eccentric metaphyseal cortical lucency with a sclerotic scalloped border, found incidentally in children, and it resolves spontaneously.
Fibrous dysplasia replaces bone with fibro-osseous tissue and gives a ground-glass appearance, with the shepherd's crook deformity of the proximal femur in polyostotic disease.
10. Metastasis and Myeloma
Metastatic disease is by far the commonest malignancy of bone in adults, and the primaries that reach it most often are breast, lung, thyroid, kidney and prostate.
Most deposits are lytic. Prostate is characteristically sclerotic, and breast can be either. The axial skeleton is affected far more than the appendicular, because red marrow persists there.
Myeloma is the important exception on bone scan. It produces punched-out lytic lesions with almost no osteoblastic reaction, so a technetium bone scan can be falsely negative, and skeletal survey or whole-body magnetic resonance imaging is used instead.
The Mirels score predicts pathological fracture in a metastatic long bone lesion, scoring site, pain, lesion type and size, with prophylactic fixation advised at a total of nine or more.
The reasoning behind prophylactic fixation is worth understanding. Fixing a bone before it breaks is a shorter operation on an intact bone with a better functional result, whereas fixing it afterwards means an emergency procedure in a patient who has already lost mobility.
11. Investigation, Staging and Margins
The plain radiograph remains the single most informative investigation, and this is unusual in modern practice. It is what answers all three of the opening questions, and no cross-sectional study replaces it for diagnosis.
The other studies each answer one specific question. Magnetic resonance imaging defines the local extent, meaning marrow involvement, soft tissue mass and the relationship to neurovascular structures, which is what determines whether limb salvage is possible.
Computed tomography of the chest stages the lungs, which is where bone sarcomas metastasise. A bone scan or positron emission tomography surveys the rest of the skeleton for skip lesions and other deposits.
Enneking staging
The Enneking system stages musculoskeletal tumours using grade, compartment and metastasis, and its central idea is the compartment, meaning an anatomical space bounded by structures that resist tumour spread, such as fascia, bone cortex and articular cartilage.
A lesion confined within a compartment is stage A and one that has breached it is stage B, with low-grade lesions stage I and high-grade stage II, and any metastasis making it stage III regardless of the rest.
Benign lesions are graded separately as latent, active or aggressive, which is why an aggressive benign lesion such as a giant cell tumour may need wider surgery than a low-grade malignancy.
Surgical margins
| Margin | What is removed |
|---|---|
| Intralesional | Through the tumour, leaving disease behind |
| Marginal | Through the reactive zone around the tumour |
| Wide | A cuff of normal tissue, within the compartment |
| Radical | The entire compartment |
The reactive zone contains satellite tumour nodules, which is exactly why a marginal excision recurs and why a wide margin is the minimum acceptable for a sarcoma.
Curettage is an intralesional procedure by definition, which is why it is acceptable for benign lesions and unacceptable for sarcoma, and why adjuvants such as phenol or a burr are added when curetting an aggressive benign lesion.
12. Biopsy Is a Surgical Decision
The biopsy of a suspected primary bone sarcoma is the single point at which an otherwise curable tumour is most often ruined.
The tract is contaminated by tumour and must be excised with the specimen, so the biopsy is placed where the definitive resection will remove it, using a longitudinal incision, avoiding neurovascular structures and avoiding crossing compartments.
It should be performed at the centre that will undertake the definitive surgery, because a badly placed biopsy can convert a limb-salvage case into an amputation.
In Indian practice the further difficulty is delay. Patients frequently present after months of local treatment for presumed sprain or arthritis, with a large tumour and sometimes a pathological fracture, which reduces both the chance of limb salvage and survival.
The practical rule that follows applies well beyond oncology. Persistent bone pain that wakes a patient at night, or that does not settle along the expected course of a sprain, earns a radiograph rather than another course of analgesia, and that single habit catches most of the tumours that are currently found late.
13. Worked Examples
Example 1. A 14-year-old has knee pain and a metaphyseal lesion of the distal femur with a wide zone of transition, cloud-like density, a sunburst reaction and a Codman triangle. Diagnosis and initial treatment?
Osteosarcoma. Age, metaphyseal location around the knee, osteoid matrix and aggressive periosteal reaction together are diagnostic. After biopsy and staging including chest imaging, treatment begins with neoadjuvant chemotherapy using methotrexate, doxorubicin and cisplatin, followed by wide resection with limb salvage where feasible, then further chemotherapy. Percentage necrosis in the specimen is the strongest prognostic indicator.
Example 2. A 12-year-old has fever, a raised white cell count, a raised erythrocyte sedimentation rate, and a permeative diaphyseal lesion of the femur with onion-skin periosteal reaction. Why is antibiotic treatment alone unsafe?
Because this is Ewing sarcoma until proved otherwise. It mimics osteomyelitis almost exactly, including the systemic inflammatory features, and the diaphyseal location with lamellated periosteal reaction and a large soft tissue mass favours tumour. Biopsy is required. Histology shows small round blue cells with CD99 membrane positivity, and the EWSR1-FLI1 fusion from the translocation between chromosomes 11 and 22 confirms it.
Example 3. A 28-year-old has a lytic, eccentric, expansile lesion in the distal radial epiphysis extending to subchondral bone. Classification and treatment?
Giant cell tumour, which the 2020 WHO classification designates intermediate and locally aggressive rather than benign. Standard treatment is extended curettage with an adjuvant and cement filling. Denosumab is useful before en bloc resection of pelvic or spinal lesions but should be avoided before curettage, since the rim of new bone it induces obscures the tumour interface and increases local recurrence.
Example 4. A 62-year-old has back pain and multiple punched-out lytic skull lesions. A technetium bone scan is unremarkable. Explain.
Multiple myeloma. The bone scan detects osteoblastic activity rather than the tumour itself, and myeloma lesions are almost purely lytic with negligible osteoblastic response, so the scan is characteristically falsely negative. Skeletal survey or whole-body magnetic resonance imaging is used instead, alongside serum and urine protein electrophoresis and marrow examination.
Summary
Three questions: age, site within the bone, and what the bone is doing about it.
The zone of transition is the most useful single sign, narrow meaning slow and wide meaning fast.
Solid periosteal reaction is slow; onion-skin is intermittent; sunburst and Codman triangle mean fast.
Osteoid matrix is cloud-like; chondroid matrix shows rings and arcs.
Over 40, a destructive lesion is metastasis or myeloma until proved otherwise.
Epiphysis means chondroblastoma before physeal closure and giant cell tumour after it.
Osteosarcoma is metaphyseal around the knee in the second decade, treated with MAP chemotherapy before and after resection, with necrosis the key prognostic marker.
Ewing sarcoma is diaphyseal, permeative, febrile and radiosensitive, with CD99 positivity and the EWSR1-FLI1 fusion.
Chondrosarcoma resists chemotherapy and radiotherapy, so surgery is the treatment.
Giant cell tumour is intermediate, not benign, and denosumab helps before en bloc resection but harms before curettage.
Osteoid osteoma has night pain relieved by anti-inflammatory drugs, because the pain is prostaglandin-mediated.
Osteochondroma has cortex and medulla continuous with the host bone.
Myeloma is cold on bone scan.
The plain radiograph is still the most informative single investigation, with magnetic resonance imaging for local extent and computed tomography of the chest for metastasis.
Enneking staging turns on the compartment, and the reactive zone around a sarcoma contains satellite nodules, which is why a marginal excision recurs and a wide margin is the minimum acceptable.
A badly placed biopsy can cost the limb.
