Musculoskeletal tumour

Musculoskeletal tumours are abnormal growths arising from bone, cartilage, skeletal muscle, fat, fibrous tissue, blood vessels, or peripheral nerves. They may be benign or malignant, with malignant tumours classified as primary bone or soft tissue sarcomas or secondary (metastatic) tumours. Metastatic bone disease is far more common than primary bone malignancy, with the most frequent primary cancers originating from the breast, prostate, lung, kidney, and thyroid. Early recognition and timely referral to an orthopaedic oncology centre are essential because delayed diagnosis may adversely affect limb salvage and survival.

Pathophysiology

Musculoskeletal tumours develop through genetic mutations that disrupt normal cellular proliferation, differentiation, and programmed cell death. Benign tumours generally remain localized and grow slowly without invading surrounding tissues. Malignant tumours acquire the ability to invade adjacent structures, destroy bone or soft tissues, stimulate formation of abnormal blood vessels, and metastasize to distant organs, particularly the lungs.

Primary bone tumours often arise from osteoblasts, chondrocytes, or primitive mesenchymal cells. As the tumour enlarges, it destroys normal bone architecture, weakens cortical bone, and predisposes patients to pathological fractures. Soft tissue sarcomas infiltrate muscles, fascia, and neurovascular structures, producing progressive pain, swelling, and loss of function. Bone metastases occur when malignant cells spread through the bloodstream and establish secondary deposits within the bone marrow, causing osteolysis, osteoblastic activity, or mixed lesions that result in pain, skeletal instability, hypercalcaemia, and fractures.

Risk factors

• Previous exposure to ionizing radiation

• Genetic syndromes (e.g. Li-Fraumeni syndrome, hereditary retinoblastoma, neurofibromatosis type 1)

• Paget disease of bone

• Chronic osteomyelitis (rare association)

• Previous chemotherapy

• Increasing age (especially metastatic disease)

• History of malignancy elsewhere

Clinical presentation

Patients may present with:

• Persistent deep, aching pain, especially night pain or pain at rest (red flag)

• Progressive swelling or enlarging soft tissue mass

• Local tenderness

• Restricted joint movement or reduced limb function

• Limp or altered gait

• Pathological fracture following minimal trauma

• Neurological deficits due to nerve compression

• Constitutional symptoms (late disease):

  • Fever

  • Weight loss

  • Fatigue

  • Anaemia

  • Loss of appetite

Note: Any painful bone lesion or soft tissue mass >5 cm, enlarging, deep to fascia, or persistent for more than 4 weeks should be considered malignant until proven otherwise.

Diagnostic approach

A systematic evaluation should be performed before biopsy.

Laboratory investigations

• Complete blood count (CBC)

• Erythrocyte sedimentation rate (ESR)

• C-reactive protein (CRP)

• Serum calcium

• Serum phosphate

• Alkaline phosphatase (ALP)

• Lactate dehydrogenase (LDH)

• Liver function tests

• Renal function tests

• Serum protein electrophoresis when multiple myeloma is suspected

• Tumour markers where appropriate according to suspected primary malignancy

Imaging

• Plain radiographs (first-line investigation)

• MRI of the affected bone or soft tissue with contrast

• CT scan for cortical bone destruction and surgical planning

• CT chest for pulmonary metastases

• Bone scan or PET-CT for staging

• Ultrasound for superficial soft tissue masses

Tissue diagnosis

• Image-guided core needle biopsy (preferred)

• Open incisional biopsy when indicated

• Histopathological examination

• Immunohistochemistry

• Molecular or cytogenetic studies where available

Important: Biopsy should ideally be performed by the orthopaedic oncology team responsible for definitive treatment to avoid compromising future limb-salvage surgery.

Red flag features requiring urgent referral

• Persistent night pain

• Pain unrelated to activity

• Rapidly enlarging mass

• Mass >5 cm

• Deep-seated mass beneath fascia

• Pathological fracture

• Neurological deficits

• Unexplained constitutional symptoms

• Previous history of malignancy

Management principles

Treatment should be undertaken by a multidisciplinary team comprising orthopaedic oncologists, medical oncologists, radiation oncologists, radiologists, pathologists, physiotherapists, occupational therapists, and palliative care specialists.

Management depends on:

• Histological diagnosis

• Tumour grade

• Tumour stage

• Anatomical location

• Presence of metastases

• Patient age and performance status

Pharmacological management

Pain management

Mild to moderate pain

A: Ibuprofen (PO) 400 mg stat, then 200 mg every 8 hours for 7–14 days

OR

C: Diclofenac sodium (PO) 50 mg every 8 hours for 7–14 days

OR

D: Meloxicam (PO) 7.5–15 mg once daily for 7–14 days

Severe pain

A: Diclofenac (IM) 75 mg every 12 hours for 1–3 days

±

B: Tramadol (IM) 100 mg every 12 hours for 1–3 days

THEN

B: Tramadol (PO) 50 mg every 8 hours as required.

Gastroprotection (when prolonged NSAID therapy is required)

A: Omeprazole (PO) 20 mg once daily

OR

C: Pantoprazole (PO) 40 mg once daily

OR

S: Esomeprazole (PO) 40 mg once daily

for 2–4 weeks.

Bone-targeted therapy (metastatic bone disease)

Patients with metastatic bone disease should receive bone-modifying agents according to oncology protocols, such as:

• Bisphosphonates (e.g. zoledronic acid)

• Denosumab

after appropriate assessment of renal function, calcium status, and dental health.

Chemotherapy, targeted therapy, immunotherapy, hormonal therapy, or radiotherapy should be administered according to tumour type and oncology recommendations.

Surgical management

Treatment depends on tumour type and stage.

Benign tumours

• Observation for asymptomatic lesions

• Curettage with or without bone grafting

• Internal fixation for pathological fractures

• En bloc excision where indicated

Malignant primary tumours

• Limb-salvage surgery whenever feasible

• Wide tumour excision with negative margins

• Endoprosthetic reconstruction

• Biological reconstruction using bone grafts

• Rotationplasty in selected patients

• Amputation when limb salvage is not possible or oncologically safe

Metastatic bone disease

• Prophylactic fixation of impending pathological fractures

• Internal fixation with or without cement augmentation

• Endoprosthetic reconstruction

• Palliative decompression for spinal cord compression

Rehabilitation

• Early physiotherapy

• Occupational therapy

• Prosthetic rehabilitation following amputation

• Pain management

• Psychological counselling

• Nutritional support

• Long-term surveillance for recurrence and metastasis

Follow-up

Patients require long-term surveillance with clinical examination and appropriate imaging to detect:

• Local recurrence

• Pulmonary metastases

• Implant complications

• Functional outcomes

• Late effects of chemotherapy or radiotherapy

Prognosis

The prognosis depends on tumour histology, grade, stage at diagnosis, response to treatment, and adequacy of surgical margins. Early diagnosis and referral to specialized musculoskeletal oncology centres significantly improve limb preservation and overall survival.