Primary bone tumours

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Primary bone sarcoma is uncommon enough that the diagnostic pathway itself determines outcome. Age and site suggest a differential: osteosarcoma often arises around the knee or proximal humerus during the adolescent growth spurt, Ewing sarcoma commonly affects pelvic or diaphyseal bone, and chondrosarcoma more often involves the adult axial skeleton. Pain typically becomes persistent, occurs at rest or night and is followed by swelling. Normal early blood tests do not exclude disease.

Plain radiographs show the biological behaviour of the lesion: a narrow transition zone and intact cortex favour indolence, whereas permeative destruction, aggressive periosteal reaction, cortical breakthrough and soft-tissue mass suggest malignancy. MRI then maps longitudinal marrow, joint, muscle and neurovascular extent. Imaging must precede biopsy because the radiologist and surgeon select a route that avoids uninvolved compartments and will be excised later. A poorly placed biopsy or nail seeds tissue that otherwise could have been preserved.

Diagnosis integrates morphology, immunohistochemistry and molecular analysis. Malignant osteoid establishes osteosarcoma; EWSR1-associated fusion testing supports Ewing sarcoma but is interpreted with morphology because other tumours share rearrangements. Cartilage tumours require expert radiology-pathology correlation since a small biopsy may undergrade heterogeneous chondrosarcoma. Staging includes the lungs and skeleton and is completed before definitive local control where the patient is stable.

Treatment is histology specific. Osteosarcoma and Ewing sarcoma are systemic diseases from the outset and need specialist chemotherapy around local treatment. Wide surgery removes tumour and biopsy tract intact; reconstructive choices include endoprosthesis, allograft, biological reconstruction, rotationplasty or amputation. Radiotherapy is central to unresectable or margin-positive Ewing disease but osteosarcoma and conventional chondrosarcoma rely more heavily on surgery. Rehabilitation and late-effect care begin before the first operation, not after treatment ends.

Key points

Primary malignant bone tumours are rare; osteosarcoma peaks in adolescents, Ewing sarcoma in children and young adults, and conventional chondrosarcoma in later adulthood.
Persistent night or rest pain, focal swelling and an unexplained pathological fracture are key warning features; a remembered sports injury does not exclude sarcoma.
First-line imaging is a high-quality plain radiograph in two planes including the whole involved bone and adjacent joints.
MRI of the entire involved bone and compartment is the preferred local-staging test and must be completed before biopsy where practical.
CT chest is the standard first staging test for pulmonary metastases; bone scintigraphy or PET-based imaging assesses additional skeletal disease according to histology and protocol.
The diagnostic reference standard is image-guided core biopsy planned by the bone-sarcoma MDT so its tract can be removed with the definitive specimen.
Never perform unplanned curettage, excision or routine internal fixation of a suspicious lesion; contamination can convert a limb-sparing resection into a larger operation or amputation.
Osteosarcoma treatment usually combines multiagent chemotherapy with wide surgical resection; response is assessed by necrosis in the resection specimen.
Ewing sarcoma requires systemic multiagent chemotherapy plus surgery and or radiotherapy for local control; treatment of all metastatic sites is considered in curative protocols.
Conventional chondrosarcoma is managed mainly by complete wide resection because ordinary chemotherapy and radiotherapy have limited activity; mesenchymal and dedifferentiated subtypes differ.
A pathological fracture is immobilised and discussed with the sarcoma surgeon before any fixation; the definitive construct must be part of the oncological resection plan.
Limb salvage is preferred when a wide margin and useful function are achievable, but amputation may provide the safest margin or best function in selected cases.
Follow-up concentrates on lung relapse, local recurrence, reconstruction performance and lifelong cardiotoxic, renal, auditory, fertility and second-cancer effects.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Usually sporadic

Most osteosarcoma, Ewing sarcoma and chondrosarcoma arises without an identifiable exposure, with characteristic age and skeletal distributions guiding probability rather than proving diagnosis.

Inherited cancer predisposition

Germline RB1 and TP53 variants, RECQL4-related syndromes and selected DNA-repair disorders raise osteosarcoma risk and justify genetics review when age, phenotype or family history suggests it.

Previously abnormal or irradiated bone

Paget disease, bone infarction, chronic osteomyelitis and previous therapeutic radiation can provide a substrate for secondary osteosarcoma or another high-grade sarcoma years later.

Cartilage tumour progression

Central or peripheral atypical cartilaginous tumours and hereditary multiple exostoses can undergo malignant progression, particularly when adult pain, renewed growth or cartilage-cap thickening appears.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Osteosarcoma produces malignant osteoid
Genomically complex mesenchymal cells lay down disorganised osteoid, typically in the metaphysis of a growing long bone, and spread early through blood to lungs.
2
Ewing sarcoma is fusion driven
An EWSR1-ETS family fusion creates a small-round-cell tumour that often begins in diaphyseal bone or pelvis and can extend into a large soft-tissue mass.
3
Chondrosarcoma forms malignant cartilage
Conventional disease usually affects pelvis, shoulder girdle or proximal long bone in adults and is relatively resistant to standard cytotoxic chemotherapy and radiotherapy.
4
Compartmental growth shapes surgery
Tumour crosses cortex, elevates periosteum and tracks along marrow and neurovascular planes; wide removal must encompass tumour, reactive zone and biopsy tract without rupture.
5
Haematogenous spread dominates
Lung is the commonest metastatic site, while bone and marrow dissemination is especially relevant in Ewing sarcoma and adversely changes curative treatment intensity.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Osteosarcoma pattern

Progressive metaphyseal pain and swelling around knee or shoulder in an adolescent with mixed destruction, osteoid matrix and aggressive periosteal reaction is characteristic.

Ewing sarcoma pattern

Diaphyseal or pelvic pain, fever and a large soft-tissue component in a young person can resemble osteomyelitis and needs tissue before prolonged antibiotics.

Chondrosarcoma pattern

Deep progressive pain from pelvis, shoulder girdle or proximal long bone in an adult with rings-and-arcs mineralisation and cortical change raises concern.

Pathological fractureRed flag

Sudden inability to bear weight through a destructive lesion is an oncological emergency requiring immobilisation and sarcoma-centre planning before fixation.

Spinal or pelvic compromiseRed flag

Weakness, sphincter change, radicular pain, hydronephrosis or vascular swelling may reflect a bulky tumour threatening cord, roots or pelvic organs.

Metastatic presentation

Cough, dyspnoea, multifocal bone pain or constitutional decline can accompany lung or skeletal metastases but many pulmonary nodules remain asymptomatic.

Red flags requiring action

Persistent focal bone pain, especially pain at night or at rest, warrants imaging when it is progressive, localised or unexplained by a resolving injury.
A firm enlarging swelling fixed to bone, reduced adjacent-joint movement or focal warmth requires urgent radiography and specialist review.
A fracture after trivial force through a lytic, mixed or sclerotic lesion is pathological until proved otherwise and must not undergo routine fixation before tumour planning.
A child or young adult with metaphyseal pain and swelling around the knee or shoulder may have osteosarcoma even when symptoms began after sport.
Fever, weight loss and diaphyseal pain can mimic infection but may indicate Ewing sarcoma; neither antibiotics nor drainage should precede adequate imaging and tissue when stable.
Back pain with weakness, sensory change, gait loss or bladder or bowel dysfunction requires emergency spinal imaging and specialist decompression assessment.
A destructive bone lesion in a patient older than 40 is more likely metastasis or myeloma than primary sarcoma, but tissue strategy still matters when the diagnosis is uncertain.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line whole-bone radiographsFirst stepFirst line
Why
Characterise matrix, margins, periosteal reaction, cortical integrity and fracture in two planes including both adjacent joints.
Interpretation and limitations
Aggressive features trigger urgent sarcoma referral even when trauma occurred; compare earlier films but do not delay MRI for an evolving destructive pattern.
02
Preferred MRI for local stagingPreferred
Why
Map full intramedullary length, skip lesions, soft-tissue extension, joint involvement and relationship to nerves and vessels before biopsy.
Interpretation and limitations
Image the entire bone and compartment with tumour protocol; oedema exceeds viable tumour and the eventual biopsy path must be incorporated into planned resection.
03
Reference specialist core biopsy
Why
Establish histological and molecular diagnosis using viable tissue while preserving future oncological planes.
Interpretation and limitations
The sarcoma surgeon and interventional radiologist plan a longitudinal tract that will be excised; sample handling must support frozen tissue, cytogenetics and microbiology when relevant.
04
CT chest
Why
Detect and map pulmonary metastases before curative treatment and provide a baseline for response and later surveillance.
Interpretation and limitations
Indeterminate tiny nodules are reviewed in context and serially; do not assume every nodule is metastatic or dismiss potentially resectable lung disease.
05
Whole-skeleton staging
Why
Identify multifocal bone or marrow spread using bone scintigraphy, FDG PET-CT or whole-body MRI according to histology and protocol.
Interpretation and limitations
Ewing sarcoma and high-grade osteosarcoma require systemic staging; confirm an isolated management-changing focus when imaging is equivocal.
06
Baseline treatment fitness
Why
Measure FBC, renal, liver, bone chemistry, LDH and ALP and document cardiac, auditory, fertility and infection status before systemic therapy.
Interpretation and limitations
ALP and LDH can carry prognostic information but are not diagnostic; baseline echocardiography and audiology permit safe anthracycline and cisplatin monitoring.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Bone metastasis or myeloma

Multiple lesions, an older age, known epithelial cancer, paraprotein or marrow features favour secondary malignancy, although a solitary lesion may still need planned core biopsy.

Osteomyelitis

Infection can cause pain, fever, periosteal reaction and raised inflammatory markers; cultures and histology distinguish it because Ewing sarcoma can appear inflammatory.

Benign bone tumour

Osteochondroma, enchondroma, giant-cell tumour, simple bone cyst and non-ossifying fibroma have recognisable patterns but pain, growth or aggressive imaging features require expert reassessment.

Stress or insufficiency fracture

A linear injury pattern with compatible load history and healing supports fracture, whereas permeative destruction, soft-tissue mass or failure to improve raises tumour concern.

Musculoskeletal referred pain

Tendon, joint and radicular disorders are common, but persistent focal bony tenderness, night pain, swelling or an abnormal radiograph should end empirical treatment.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Suspicious bone lesionImage before tissue and refer before interventionFirst stepPersistent focal bone symptoms or radiography shows an aggressive or unexplained lesion.

1Obtain two-plane radiographs of the whole bone, examine swelling, joint and neurovascular function and provide safe analgesia and weight-bearing advice.
2Contact the regional bone-sarcoma service and complete tumour-protocol MRI before biopsy, with CT chest and whole-body staging arranged through the specialist team.
3DefinitiveUse MDT-planned image-guided core biopsy with a resectable tract, then integrate expert pathology, molecular results and stage before any definitive operation.

02Pathological fractureProtect the limb without spreading tumourA fracture occurs through a possible primary bone malignancy.

1Immobilise, control pain, document skin and distal neurovascular status and investigate the lesion and whole bone urgently.
2DefinitiveDiscuss immediately with the bone-sarcoma surgeon and avoid a nail, plate, curettage or haematoma evacuation until diagnosis and definitive resection strategy are agreed.
3Plan biopsy and fracture reconstruction together, considering neoadjuvant treatment, tumour-bearing bone removal, limb salvage and amputation according to contamination and function.

03Osteosarcoma or Ewing sarcomaCombine systemic and complete local treatmentExpert pathology confirms a chemotherapy-sensitive high-grade bone sarcoma.

1Complete lung and skeletal staging, baseline organ testing, central access, fertility preservation and age-appropriate psychosocial preparation before protocol therapy.
2DefinitiveGive histology- and age-specific induction chemotherapy and reassess local and metastatic response without postponing definitive surgery beyond the protocol window.
3Remove tumour and biopsy tract with a wide margin, use postoperative histological response and margins to complete chemotherapy and treat selected lung, bone or margin sites surgically or with radiotherapy.

04ChondrosarcomaPrioritise en-bloc surgical clearanceExpert review confirms a resectable conventional central or peripheral chondrosarcoma.

1Correlate MRI, CT matrix and multiple representative cores because heterogeneous cartilage tumours can be undergraded by a small sample.
2Perform wide en-bloc resection without tumour rupture, planning pelvic, chest-wall or limb reconstruction in a specialist sarcoma centre.
3Reserve systemic therapy and radiation for responsive rare subtypes, unresectable sites or trials and use long surveillance because late local and lung relapse occurs.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Treats presumed micrometastatic disease before and after wide resection and permits pathological assessment of chemotherapy response.

MAP chemotherapy for osteosarcoma

Use specialist-protocol high-dose methotrexate with folinic-acid rescue, doxorubicin and cisplatin in suitable younger patients; exact doses, cycles, hydration and rescue are determined by the national age-specific sarcoma protocol.

Monitor methotrexate clearance, renal and liver function, mucositis, marrow, infection, cisplatin hearing and kidney injury and cumulative anthracycline cardiac exposure; delayed clearance is an emergency.

Provides systemic control around surgery or radiotherapy for localised and selected metastatic Ewing sarcoma.

VDC/IE chemotherapy for Ewing sarcoma

Alternate specialist cycles of vincristine, doxorubicin and cyclophosphamide with ifosfamide and etoposide at protocol-defined intervals, using mesna, hydration and growth-factor support as specified.

Watch febrile neutropenia, haemorrhagic cystitis, ifosfamide encephalopathy and renal tubular injury, neuropathy, infertility, secondary leukaemia and lifetime anthracycline dose.

Controls severe tumour or fracture pain while immobilisation, imaging and definitive oncological treatment are organised.

Analgesia while diagnosis is secured

Use regular paracetamol and, when needed, a titrated immediate-release oral opioid with laxative and antiemetic; avoid intramuscular injections through a potential surgical compartment.

Do not let symptom improvement delay referral; assess sedation, respiratory risk, renal function, constipation and driving, and avoid NSAIDs when renal-toxic chemotherapy, bleeding or surgery makes them unsafe.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Pathological fracture

Cortical destruction can produce sudden pain and instability; haematoma and fixation may spread tumour across compartments and make later limb salvage more difficult.

Pulmonary and skeletal metastases

Micrometastatic lung disease may exist at diagnosis and can later form resectable nodules or diffuse progression, while bone spread causes pain and further fracture.

Neurovascular and organ compromise

Pelvic, spinal or bulky limb tumours can compress nerves, vessels, ureters, bowel or cord, producing irreversible function loss without urgent multidisciplinary control.

Treatment-related late effects

Anthracycline cardiomyopathy, cisplatin hearing or renal injury, infertility, second cancer, prosthetic infection and mechanical failure require lifelong risk-adapted surveillance.

Functional and psychological loss

Resection, amputation or reconstruction can alter gait, growth, work, sport, body image and independence even when oncological treatment is successful.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

During chemotherapy, review blood counts, fever, renal and liver function, hydration, methotrexate levels when used, hearing, neuropathy and cumulative cardiac exposure according to protocol.
After local treatment, inspect wounds and reconstruction, document neurovascular and joint function and begin supervised strength, gait and prosthetic rehabilitation.
Surveillance combines clinical examination and chest imaging with local radiographs or MRI at risk-based intervals, with the greatest relapse intensity in early years but continued long-term review.
Assess any new cough, focal pain, swelling or loss of prosthetic function promptly rather than waiting for the next routine surveillance visit.
Monitor growing children for limb-length discrepancy and deformity and adults for endoprosthetic loosening, infection, wear, fracture and revision needs.
Provide lifelong echocardiographic, renal, auditory, endocrine, fertility and second-malignancy follow-up according to cumulative treatment exposures.
Review education, work, sport, body image, driving, mental health and peer support as measurable survivorship outcomes alongside disease control.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

The biopsy is part of the operation

Its tract is contaminated by definition and must lie where it can be removed en bloc without sacrificing an otherwise uninvolved compartment.

Trauma often reveals rather than causes tumour

Exercise draws attention to pre-existing pain or weak bone; an injury story should not explain persistent night pain or aggressive radiography away.

A normal blood panel does not reassure

Most localised bone sarcomas have no specific serum marker, and ALP or LDH may remain normal despite substantial disease.

Cartilage grading needs the whole picture

Histological blandness in one core can coexist with higher-grade areas, so symptoms, imaging and expert pathology are inseparable.

Limb salvage is not automatically better function

Margin safety, expected revisions, nerve loss, rehabilitation and patient goals determine whether reconstruction or amputation offers the stronger outcome.

Late surveillance is genuinely lifelong

Relapse may be late in chondrosarcoma, while prostheses and cardiotoxic, fertility and second-cancer risks persist decades after cure.

11Common pitfallsFrequent interpretation and management errors.

01
Attributing persistent night pain to sport without radiography.
02
Reassuring from normal inflammatory markers, ALP or full blood count.
03
Biopsying before MRI defines the tumour compartment and safest tract.
04
Using a transverse incision or approaching through uninvolved muscle planes.
05
Fixing a pathological fracture with an intramedullary nail before sarcoma review.
06
Curetting a presumed benign cartilage lesion despite adult pain and aggressive imaging.
07
Treating Ewing-like fever and periosteal reaction as infection without adequate tissue.
08
Assuming all primary bone sarcomas share the same chemotherapy sensitivity.
09
Focusing on the limb while omitting CT chest and whole-skeleton staging.
10
Ending follow-up after chemotherapy without reconstruction and late-effect surveillance.