• Clinical science

Malignant bone tumors

Summary

Malignant bone tumors can be classified as primary (arising from abnormal bone or cartilage cells) or secondary (bone metastases of other tumors). The most common primary bone tumors are osteosarcomas, Ewing sarcomas, and chondrosarcomas. These tumors differ with regard to primary localization, radiographic characteristics, and the patient age at which they usually develop. Progressive, localized pain that worsens at night or with physical activity is common and usually accompanied by swelling. In Ewing sarcoma and osteosarcoma, symptoms often first manifest after an injury. Diagnosis is confirmed by imaging and biopsy. Depending on the type and stage of the tumor, chemotherapy, radiation therapy, and/or definitive surgical resection may be required. Bone tumors may also occur secondary to metastases of other primary cancers. The metastases are commonly detected in the spine and pelvis and usually arise from the lung, breast, and prostate cancer. Treatment focuses on the underlying malignancy and additional management of pain and prevention of fractures related to the metastases.

Ewing sarcoma

  • Description: : highly malignant bone tumor arising from neuroectodermal cells; ; associated with various chromosomal translocations of the EWSR1 gene (chromosome 22)
  • Epidemiology
    • Incidence: peak at 10–15 years
    • Sex: ♂ > ♀
    • Ethnicity: primarily affects whites
  • Clinical features
    • Frequently first manifests with localized pain (progressive, worsens at night), hyperthermia, and swelling after trauma to the bone (tissue mass that is tender to palpation and accompanied by erythema)
    • B symptoms are common
  • Localization
  • Diagnostics
  • Treatment
    • Surgery; (definitive resection) plus neoadjuvant and adjuvant polychemotherapy
    • Additionally: neoadjuvant and/or adjuvant radiation therapy
  • Prognosis
    • Extremely aggressive, early metastasis
    • Five-year survival rate of ∼ 70%

References:[1][2][3][4][5][6]

Osteosarcoma

Osteosarcomas are usually resistant to radiation therapy!

References:[7][3][6][8][9][10]

Chondrosarcoma

  • Description: malignant tumor arising from mesenchymal cells that produce cartilage
  • Etiology
  • Epidemiology
    • Age: usually > 50 years
    • Sex: ♂ > ♀
  • Clinical findings
    • Deep, dull pain (worsens at night, insidious progression over months to years)
    • Local swelling
    • Pathological fractures
    • Neurovascular disturbances and/or limited range of motion
  • Localization: mainly pelvis, ribs, proximal femur, and proximal humerus
  • Diagnostics
    • Conventional x-ray or CT
      • Osteolysis with moth-eaten appearance
      • Calcifications (rings and arcs calcification, popcorn calcification)
      • Endosteal scalloping and cortical breach with infiltration of soft tissue
    • MRI: rim-like contrast enhancement
    • Biopsy
  • Treatment
  • Prognosis
    • Five-year survival rate of ∼ 50–60%
    • Late recurrences are possible → regular follow-ups for 10 years

References:[11][12][13]

Chordoma

References:[14][15]

Diagnostics

Imaging

General approach

  • Detection and evaluation of possible primary bone tumors
    • Plain radiography (initial test of choice): fast and efficient overview, detection of bone lesions and indication of probable histological type (malignant or benign)
    • CT: beneficial in areas with complex bony structures; may be required to evaluate bone stability
    • MRI: assesses the extent of soft tissue and bone marrow involvement
    • Scintigraphy: measures metabolic activity of bone lesions
  • Detection of metastases (See secondary malignancies of the bone below.)

Radiographic signs of malignant bone tumors

Biopsy

  • Indications: confirmation of radiologic diagnosis ; guidance of therapeutic procedures
  • Techniques: open biopsy, needle biopsy (e.g., fine needle aspiration)

Laboratory tests

References:[16][17][18][19]

Differential diagnosis of primary malignant bone tumors

Age group Main localization Radiographic characteristics Treatment Five-year survival rate
Ewing sarcoma
  • Children/adolescents
  • Onion skin appearance
  • Surgery
  • Polychemotherapy
  • Radiation
  • ∼ 70%
Osteosarcoma
  • Adolescents/young adults
  • Surgery
  • Polychemotherapy
  • ∼ 70%
Chondrosarcoma
  • Adults
  • Moth-eaten appearance
  • Endosteal scalloping
  • Intralesional calcifications
  • Surgery
  • ∼ 50-60%

Differential diagnosis of bone pain in children

  • Benign bone conditions
  • Growing pains
    • Epidemiology: : affects up to 35% of all children; most commonly seen at 3–12 years of age
    • Etiology: unknown
    • Clinical features
      • Episodic, bilateral pain that affects predominantly the lower extremities (shins, calves, thighs, popliteal fossa)
      • Pain typically occurs late in the day or during the night → children awaken from sleep
      • May be mild to severe and lasts for a few minutes to several hours; usually resolves by morning
      • Pain is not present during the day or activities
    • Diagnosis: clinical; imaging shows no abnormalities and is not indicated
    • Treatment: reassurance; acetaminophen/NSAIDs and massages during acute pain episodes may alleviate symptoms
    • Prognosis: : good; most cases resolve spontaneously by late childhood

References:[8][13][20]

Secondary malignancies of the bone (bone metastasis)

Description

Clinical findings

Diagnostics

Approach

  • Imaging is generally only performed in patients with primary malignancies who have clinical signs or laboratory findings (e.g., elevated alkaline phosphatase, hypercalcemia) indicating metastatic bone disease
  • Biopsy is performed to confirm the diagnosis when imaging is insufficient or the patient has no known history of cancer

Laboratory

  • Elevated serum calcium

Radiographic imaging

  • Choice of imaging studies depends on
    1. The location of the suspected lesion and the clinical presentation
    2. The most likely underlying primary tumor
  • For suspected spinal lesions:
    • Contrast-enhanced MRI (first-line modality; ); used to detect tumor extension and possible spinal cord compression
    • CT may be performed to assess vertebral bone integrity
  • For suspected extremity lesions:
    • Conventional X-ray (initial test) However, lesions are only visible if extensive density loss occurs and periosteal reactions are often scarce to nonexistent.
    • Followed by CT or MRI if pathological fracture is identified or suspected for operative planning
  • Whole-body skeletal imaging: indicated if a metastatic lesion is identified to detect additional, asymptomatic sites of metastasis

Biopsy

  • Preferably taken from a soft tissue mass at the afflicted site, otherwise from an accessible bone where biopsy does not cause lasting impairment of motility or stability
  • In case of an isolated lesion, it should be presumed to be a primary tumor unless proven otherwise.

Treatment

The choice of treatment generally depends on the underlying primary malignancy and stage of disease.

References:[6][21][22][17][23][24]